MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Journal of Neuroscience Research' source. Tue, 07 Feb 2012 07:05:44 +0100 http://www.medworm.com/index.php?rid=5657868&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22831 AbstractNeuronal ceroid lipofuscinoses (NCLs) are a group of hereditary childhood diseases characterized mainly by lipopigment accumulation and a multisystemic pattern of symptoms including mental retardation, seizures, motor impairment, and blindness. The mnd mouse, carrying a mutation in the Cln8 gene, has been proposed as a model of epilepsy with mental retardation (EPMR, ornorthern epilepsy). We recently showed neuronal hyperexcitability and seizure hypersusceptibility in mnd mice. To elucidate the cellular mechanisms related to hippocampal hyperexcitability, the glutamatergic transmission and the expression of postsynaptic glutamate receptors were investigated in hippocampus. A significant increase in either spontaneous or KCl‐stimulated overflow of [3H]D‐aspartate was found in mn... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5657868 Sat, 04 Feb 2012 12:17:27 +0100 5657868 http://www.medworm.com/index.php?rid=5657871&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.23022 We report that endogenous sealing in both preparations is enhanced by Ca2+‐containing solutions and is decreased by Ca2+‐free solutions containing antioxidants such as dithiothreitol (DTT), melatonin (MEL), methylene blue (MB), and various toxins that decrease vesicular interactions. In contrast, the fusogen polyethylene glycol (PEG) at 10–50 mM artificially seals the cut ends of B104 cells and rat sciatic axons within seconds and is not affected by Ca2+ or any of the substances that affect endogenous sealing. At higher concentrations, PEG decreases sealing of transected axons and disrupts the plasmalemma of intact cells. These PEG‐sealing data are consistent with the hypothesis that lower concentrations of PEG directly seal a damaged plasmalemma. We have considered these and other... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5657871 Fri, 03 Feb 2012 05:00:00 +0100 5657871 http://www.medworm.com/index.php?rid=5657870&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.23023 We report that, after complete cut‐ or crush‐severance of rat sciatic nerves, morphological continuity, action potential conduction, and behavioral functions can be consistently (>98% of trials), rapidly (minutes to days), dramatically (70–85% recovery), and chronically restored and some Wallerian degeneration prevented. We assess axoplasmic and axolemmal continuity by intra‐axonal dye diffusion and action potential conduction across the lesion site and amount of behavioral recovery by Sciatic Functional Index and Foot Fault tests. We apply well‐specified sequences of solutions containing FDA‐approved chemicals. First, severed axonal ends are opened and resealing is prevented by hypotonic Ca2+‐free saline containing antioxidants (especially methylene blue) that inhibit pla... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5657870 Fri, 03 Feb 2012 05:00:00 +0100 5657870 http://www.medworm.com/index.php?rid=5657869&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.23005 AbstractAlthough more than 100 drugs have been examined clinically, tissue plasminogen activator remains the only drug approved for the treatment of acute ischemic stroke. Since the discovery of ischemic tolerance, it has been widely recognized that the brain possesses an endogenous protective machinery to protect against ischemic stress. Recent studies have clarified that both the upregulation of neuroprotective signaling and the downregulation of inflammatory or apoptotic pathways are involved equally in the acquisition of ischemic tolerance. The triggering stimuli for ischemic stresses are divided into hypoxic, oxidant/inflammatory, and glutamate stress. Glutamate stress, particularly the synaptic stimulation of the N‐methyl‐D‐aspartate receptor, leads to activation of the cAMP re... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5657869 Fri, 03 Feb 2012 05:00:00 +0100 5657869 http://www.medworm.com/index.php?rid=5626064&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22828 AbstractMutations in the parkin gene underlie a familial form of Parkinson's disease known as autosomal recessive juvenile Parkinsonism (AR‐JP). Dysfunction of parkin, a ubiquitin E3 ligase, has been implicated in the accumulation of ubiquitin proteasome system‐destined substrates and eventually leads to cell death. However, regulation of parkin enzymatic activity is incompletely understood. Here we investigated whether the ubiquitin E3 ligase activity of parkin could be regulated by neddylation. We found that parkin could be a target of covalent modification with NEDD8, a ubiquitin‐like posttranslational modifier. In addition, NEDD8 attachment caused an increase of parkin activity through the increased binding affinity for ubiquitin‐conjugating E2 enzyme as well as the enhanced fo... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5626064 Wed, 25 Jan 2012 14:06:45 +0100 5626064 http://www.medworm.com/index.php?rid=5605594&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22830 AbstractGrowing evidence suggests that decreased brain‐derived neurotrophic factor (BDNF) levels are associated with Alzheimer's disease (AD) pathogenesis. Therefore, BDNF gene therapy is considered to be a promising therapeutic strategy for treating AD. Sendai virus (SeV) is a type I parainfluenza virus that does not interact with host chromosomes because of its strict cytoplasmic life cycle. Although SeV is nonpathogenic in primates, including humans, its infectivity for neurons is strong. Here we demonstrate that SeV vectors effectively infected neurons, even though they were injected into subcortical white matter. Moreover, SeV vectors significantly induced BDNF expression, ameliorating synaptic degeneration and memory deficits in a transgenic mouse model of AD (Tg2576). This is the ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5605594 Thu, 19 Jan 2012 12:23:37 +0100 5605594 http://www.medworm.com/index.php?rid=5605602&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22778 AbstractOxidative stress is considered to be one of the main causes of neural damage after injury. However, little is known about the changes in mRNA expression of antioxidant molecules that occur after injury and regeneration of the peripheral nerve. In the present study, the rat median nerve was transected, and transcriptional changes were studied at day 6 and day 12 after injury in both the proximal and the distal stumps, in the absence or presence of microsurgical repair. The expression profiles of the following genes were investigated: three metallothionein isoforms (MT‐1, MT‐2, and MT‐3), the main antioxidant enzymes (catalase, superoxide dismutase, and glutathione‐S‐transferase), and the marker of cellular damage poly(ADP‐ribose) polymerase‐1 (PARP‐1). The results sh... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5605602 Wed, 18 Jan 2012 05:00:00 +0100 5605602 http://www.medworm.com/index.php?rid=5605601&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.23001 AbstractRett syndrome (RTT) is a severe neurodevelopmental disorder caused by mutations in the gene MECP2 encoding the methyl‐CpG binding protein 2. This genetic disease affects predominantly girls and is characterized by a period of normal development that lasts for 8–18 months, followed by neurologic regression affecting both motor and mental abilities. Previous studies performed on brains from RTT subjects and Mecp2‐deficient mice showed striking changes in neuronal maturation and dendritic arborization. Recently, we showed that expression of stathmin‐like 2 (STMN2) was significantly reduced in fibroblasts from RTT patients, and similar results were obtained in the cerebellum of Mecp2‐deficient mice. Because assembly and dynamics of microtubules are known to be modulated by ST... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5605601 Wed, 18 Jan 2012 05:00:00 +0100 5605601 http://www.medworm.com/index.php?rid=5605600&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.23003 AbstractHerpes simplex virus type 1 (HSV‐1) is a neurotropic virus that remains latent in host neurons. Viral DNA replication is a highly structured process in which the redistribution of nuclear proteins plays an important role. Although tau is most widely known as a microtubule‐associated protein found in a hyperphosphorylated state in the brains of patients with Alzheimer's disease (AD), this protein has also been detected at other sites such as the nucleolus. Here, we establish that HSV‐1 infection gives rise to an increase in tau phosphorylation and that hyperphosphorylated tau accumulates in the nucleus, forming defined structures in HSV‐1‐infected neuronal cells reminiscent of the common sites of viral DNA replication. When tau expression in human neuroblastoma cells was s... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5605600 Wed, 18 Jan 2012 05:00:00 +0100 5605600 http://www.medworm.com/index.php?rid=5605599&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.23006 AbstractPerfusion of 4‐aminopyridine (4‐AP) by microdialysis in the hippocampus produces intense epileptiform behavioral and electrical activity and neurodegeneration, resulting from a stimulated release of glutamate from nerve endings. In contrast, accumulation of extracellular glutamate by blockade of its transport in vivo in anesthetized rats is innocuous, and studies in vitro in brain slices suggest that under these conditions glutamate may activate presynaptic group III metabotropic glutamate receptors (mGluRs) and inhibit its own release. Therefore, using microdialysis, EEG recording, and histological evaluation, we studied the effect of increased endogenous extracellular glutamate by blockade of its transport with pyrrolidine dicarboxylic acid (PDC) on the excitotoxic action of ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5605599 Wed, 18 Jan 2012 05:00:00 +0100 5605599 http://www.medworm.com/index.php?rid=5605598&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.23007 This study suggests that pharmacological normalization of DYRK1A activity may have a potential role in DS therapy. © 2012 Wiley Periodicals, Inc. (Source: Journal of Neuroscience Research) Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5605598 Wed, 18 Jan 2012 05:00:00 +0100 5605598 http://www.medworm.com/index.php?rid=5605597&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22824 AbstractIschemic brain injury is widely modeled in vitro with paradigms of oxygen‐glucose deprivation (OGD), which leads to cell death. The prevention and attenuation of brain injury by the tetracycline antibiotic minocycline has been attributed largely to suppression of microglial activation, but its benefits in oligodendrocyte cells have not been well characterized. Using primary cultures of rat oligodendroglial precursor cells (OPC) exposed to OGD, we investigated the direct effects of minocycline on the survival, proliferation, and maturation of oligodendroglial lineage cells. OGD for 2 hr caused a decrease in the total number of OPC and the amount of proliferating progenitors by 50%, which was attenuated by inclusion of minocycline. The reduced numbers of immature oligodendroglial c... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5605597 Wed, 18 Jan 2012 05:00:00 +0100 5605597 http://www.medworm.com/index.php?rid=5605596&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22825 In this study, the efficacy of novel, long‐circulating, polyethylene‐glycol‐coated liposomes encapsulating prednisolone was compared with free prednisolone in the treatment of mdx mice, a well‐established animal model for DMD. Using an objective and sensitive computerized 24‐hr detection system of voluntary wheel‐running in single cages, we demonstrate a significant impairment of the running performance in mdx compared with black/10 control mice aged 3–6 weeks. Treatment with liposomal or free prednisolone did not improve running performance compared with saline control or empty liposomes. Histopathological parameters, including the rate of internalized nuclei and fiber size variation, and mRNA and protein expression levels of transforming growth factor (TGF)‐β and monocyt... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5605596 Wed, 18 Jan 2012 05:00:00 +0100 5605596 http://www.medworm.com/index.php?rid=5605595&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22826 AbstractRemyelination of the central nervous system in multiple sclerosis patients is often incomplete. Remyelination depends on normal oligodendrogenesis and the differentiation of oligodendrocyte precursor cells (OPC) into mature oligodendrocytes (OL). Inhibitor of DNA binding (ID), a transcription factor, is thought to inhibit oligodendrogenesis and the differentiation of OPC. This Mini‐Review aims to reveal the roles of and mechanisms used by IDs (mainly ID2) in this process. An interaction between ID2 and retinoblastoma tumor suppressor is responsible for the cell cycle transition from G1 to S. The translocation of ID2 between the nucleus and cytoplasm is regulated by E47 and OLIG. An interaction between ID2 and OLIG mediates the inhibitory effects of bone morphogenic proteins and G... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5605595 Wed, 18 Jan 2012 05:00:00 +0100 5605595 http://www.medworm.com/index.php?rid=5557384&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22798 AbstractThe peripheral taste system presents an excellent model for studying the consequences of neural injury, for the damaged nerve and sensory cells and the neighboring, intact neural cells. Sectioning a primary afferent nerve, the chorda tympani (CT), rapidly recruits neutrophils to both sides of the tongue. The bilateral neutrophil response induces transient functional deficits in the intact CT. Normal function is subsequently restored as macrophages respond to injury. We hypothesized that macrophages produce the proinflammatory cytokine interleukin (IL)‐1, which contributes to the maintenance of normal taste function after nearby injury. We demonstrate that IL‐1β protein levels are significantly increased on the injured side of the tongue at day 2 after injury. Dietary sodium de... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5557384 Mon, 02 Jan 2012 21:36:57 +0100 5557384 http://www.medworm.com/index.php?rid=5535248&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22823 AbstractTo survive, cells must rapidly repair (seal) plasmalemmal damage. Cytosolic oxidation has been shown to increase cell survival in some cases and produce cell death in other protocols. An antioxidant (melatonin; Mel) has been reported to decrease the probability of sealing plasmalemmal damage. Here we report that plasmalemmal damage produces cytosolic oxidation, as assayed by methylene blue (MB) color change in rat B104 hippocampal cells. Plasmalemmal sealing is affected by duration of Ca2+ deprivation and length of exposure to, and concentration of, oxidizing agents such as H2O2 and thimerosal (TH). Cytosolic oxidation by 10 μM to 50 mM H2O2 or 100 μM to 2 mM TH increases the probability of Ca2+‐dependent plasmalemmal sealing, whereas higher concentrations of H2O2 decrease seal... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5535248 Sat, 24 Dec 2011 00:47:02 +0100 5535248 http://www.medworm.com/index.php?rid=5535256&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22812 AbstractThe aim of this study was to investigate the effect of vagus nerve stimulation (VNS) on infarct volume and neurological recovery up to 3 weeks following transient focal cerebral ischemia. Transient ischemia was produced by filament occlusion of the proximal middle cerebral artery (MCA) in rats. The right vagus nerve was stimulated starting 30 min after MCA occlusion and consisted of 30‐sec pulse trains (20 Hz) delivered to the animal's right vagus nerve every 5 min for a total period of 60 min (n = 10). All the procedures were duplicated, but no stimulus was delivered, in a control group (n = 10). Neurological evaluations were performed in all animals at 24 hr, 48 hr, 1 week, 2 weeks, and 3 weeks after MCA occlusion; animals were euthanized; and neuronal damage was evaluated in h... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5535256 Thu, 22 Dec 2011 05:00:00 +0100 5535256 http://www.medworm.com/index.php?rid=5535255&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22813 AbstractMotor neurons (MNs) are designated as alpha/gamma and fast/slow based on their target sites and the types of muscle fibers innervated; however, few molecular markers that distinguish between these subtypes are available. Here we report that osteopontin (OPN) is a selective marker of alpha MNs in the mouse spinal cord. OPN was detected in approximately 70% of postnatal choline acetyltransferase (ChAT)‐positive MNs with relatively large somas, but not in those with smaller somas. OPN+/ChAT+ MNs were also positive for NeuN, an alpha MN marker, but were negative for Err3, a gamma MN marker. The size distribution of OPN+/ChAT+ cells was nearly identical to that of NeuN+/ChAT+ alpha MNs. Group Ia proprioceptive terminals immunoreactive for vesicular glutamate transporter‐1 were selec... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5535255 Thu, 22 Dec 2011 05:00:00 +0100 5535255 http://www.medworm.com/index.php?rid=5535254&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22814 This study focuses on the identification and functional analysis of novel miRNAs in rat dorsal root ganglia (DRGs) following sciatic nerve resection, which is a classic model for studying peripheral nerve injury and regeneration. By using Solexa sequencing, computational analysis, Q‐PCR verification, and Dicer knockdown assay, 114 novel miRNAs in rats were identified, of which 51 novel miRNAs were first reported in rat DRGs, and 63 novel miRNAs were produced at days 1, 4, 7, and 14 following sciatic nerve resection. We further predicted target genes of these miRNAs and analyzed the biological processes in which they were involved. The identified biological processes were consistent with the time frame of peripheral nerve injury and regeneration, revealing that these miRNAs were genuine m... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5535254 Thu, 22 Dec 2011 05:00:00 +0100 5535254 http://www.medworm.com/index.php?rid=5535253&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22817 AbstractNicotine in tobacco smoke is thought to stimulate sensory nerve fibers by receptors that are located on airway epithelial cells and on terminal branches of C‐fiber afferents, but the exact neurochemical substrate that mediates the sensory effects of nicotine associated with cigarette smoking is not clear. ATP and nitric oxide (NO) have both been implicated in lung responsiveness to airborne chemicals such as nicotine. However, the neuroanatomical and functional relationships between nicotinic acetylcholine receptors (nAChRs), purinergic signaling, and NO are not known, and the main source of NO in the airways is not clear. In the present study, we performed RT‐PCR to confirm the presence of mRNA for all three isoforms of nitric oxide synthase (NOS), neuronal (n‐NOS), endothel... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5535253 Thu, 22 Dec 2011 05:00:00 +0100 5535253 http://www.medworm.com/index.php?rid=5535252&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22818 AbstractIn the brain, Na+/H+ exchanger‐1 (NHE‐1) activation has a significant impact on ischemic injury, and, in recent studies, NHE‐1 inhibition has been found to protect neurons from ischemic injury. This protective effect has been ascribed to the prevention of apoptosis, but neuronal cell death following ischemia is a consequence of both necrotic and apoptotic cell death. Here, we evaluated the ability of the potent NHE‐1 inhibitor cariporide to prevent necrotic cell death in an in vitro model of excitotoxic neuronal death. Cariporide (100 nM) was found to reduce both glutamate‐induced necrotic and apoptotic neuronal cell death. Ca2+ concentrations were observed to peak twice in cytosol and mitochondria in cultured neuronal cells after glutamate exposure, and cariporide was fo... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5535252 Thu, 22 Dec 2011 05:00:00 +0100 5535252 http://www.medworm.com/index.php?rid=5535251&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22819 AbstractMercury is an environmental toxicant that can disrupt brain development. However, although progress has been made in defining its neurotoxic effects, we know far less about available therapies that can effectively protect the brain in exposed individuals. We previously developed an animal model in which we defined the sequence of events underlying neurotoxicity: Methylmercury (MeHg) injection in postnatal rat acutely induced inhibition of mitosis and stimulated apoptosis in the hippocampus, which later resulted in intermediate‐term deficits in structure size and cell number. N‐acetyl cysteine (NAC) is the N‐acetyl derivative of L‐cysteine used clinically for treatment of drug intoxication. Here, based on its known efficacy in promoting MeHg urinary excretion, we evaluated N... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5535251 Thu, 22 Dec 2011 05:00:00 +0100 5535251 http://www.medworm.com/index.php?rid=5535250&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22820 AbstractMany therapies that have been developed for acute spinal cord injury (SCI) either influence or are influenced by posttraumatic inflammation. Many such therapies have reportedly produced promising neurologic benefits in animal models of SCI, but demonstrating convincing efficacy in human clinical trials has remained elusive. This discrepancy may be related in part to differences in the inflammatory response to SCI between human patients and the widely studied rodent models. Our objectives were, therefore, to establish the time course of inflammatory cytokine release in the spinal cord of rats after a thoracic contusion, to determine whether the cytokine release was injury dependent, and to correlate these findings with those that we have recently reported for the cerebrospinal fluid... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5535250 Thu, 22 Dec 2011 05:00:00 +0100 5535250 http://www.medworm.com/index.php?rid=5535249&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22821 AbstractPersistent changes in behavior and psychological function that occur as a consequence of exposure to drugs of abuse are thought to be mediated by the structural plasticity of specific neural circuits such as the brain's dopamine (DA) system. Changes in dendritic morphology in the nucleus accumbens (NAc) accompany drug‐induced enduring behavioral and molecular changes, yet ultrastructural changes in synapses following repeated exposure to drugs have not been well studied. The current study examines the role of DA D3 receptors in modulating locomotor activity induced by both acute and repeated methamphetamine (METH) administration and accompanying ultrastructural plasticity in the shell of NAc in mice. We found that D3 receptor mutant (D3−/−) mice exhibited attenuated acute loc... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5535249 Thu, 22 Dec 2011 05:00:00 +0100 5535249 http://www.medworm.com/index.php?rid=5521723&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22805 AbstractA novel type of adult neural precursor cells (NPCs) has been isolated from the subventricular zone of the mouse 6 hr after animal death (T6‐NPCs). This condition is supposed to select hypoxia‐resistant cells of scientific and clinical interest. Ionic channels are ultimately the expression of the functional maturation of neurons, so the aim of this research was to characterize the pattern of the main voltage‐dependent ionic channels in T6‐NPCs differentiating to a neuronal phenotype, comparing it with NPCs isolated soon after death (T0‐NPCs). T6‐ and T0‐NPCs grow in medium containing epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Differentiation was performed in small wells without the addition of growth factors, in the presence of adhesion mo... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5521723 Tue, 20 Dec 2011 23:47:25 +0100 5521723 http://www.medworm.com/index.php?rid=5521733&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22801 In this study, the protective effect of sodium orthovanadate (SOV) on BBB disruption was investigated in SAH using the endovascular perforation model. Fifty‐five rats were randomly assigned to sham‐operated, SAH treated with saline (as a vehicle), or 10 mg/kg SOV groups and were evaluated for neurofunction and Evans blue dye extravasation. The phosphorylation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and mitogen‐activated protein kinase (MAPK) and the expression of matrix metalloproteinase‐9 (MMP‐9), occludin, and collagen‐IV were examined by Western blot analyses. Cell death among endothelial cells was revealed by immunofluorescence and terminal deoxynucleotidyl transferase‐mediated uridine 5′‐triphosphate‐biotin nick end‐labeling staining. SO... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5521733 Tue, 20 Dec 2011 05:00:00 +0100 5521733 http://www.medworm.com/index.php?rid=5521732&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22802 AbstractPatients affected by peroxisomal disorders commonly present neurologic dysfunction and brain abnormalities, whose neuropathology is poorly understood. Given that high sustained concentrations of pristanic acid (Prist) are found in the brain of these patients, it is conceivable that this complex branched‐chain fatty acid is neurotoxic. Therefore, the present work investigated the in vitro effects of Prist at similar concentrations found in plasma of affected patients with some peroxisomal disorders on important parameters of energy homeostasis, including respiratory parameters determined by oxygen consumption, membrane potential (ΔΨm), NAD(P)H content, and swelling in mitochondrial preparations obtained from brain of young rats using glutamate plus malate or succinate as respira... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5521732 Tue, 20 Dec 2011 05:00:00 +0100 5521732 http://www.medworm.com/index.php?rid=5521731&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22804 AbstractDifferentiation and self‐renewal are two primary properties that characterize stem cells. Differentiation of neural stem/precursor cells (NSPCs) gives rise to multiple neural lineages, including neurons, astrocytes, and oligodendrocytes. Self‐renewal, by definition, signifies the progressive growth of cells, while preserving an undifferentiated state. A large number of interdependent factors, including transcription factors, epigenetic control, and micro‐RNA regulators, modulate these opposing processes without disrupting the regular neural network. The epigenetic modification of developmental genes, including alterations in DNA methylation, histone modifications, polycomb gene group and noncoding RNA expression, which are passed on through successive cell divisions, has prov... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5521731 Tue, 20 Dec 2011 05:00:00 +0100 5521731 http://www.medworm.com/index.php?rid=5521730&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22806 AbstractThyroid hormones modulate the physiology of the hippocampus in humans, where glutamate plays an important role as neurotransmitter. The aim of this work was to study the effect of hypothyroidism on hippocampal glutamate extracellular levels, release, uptake, and synthesis. The effects of PDC (a glutamate transporter inhibitor) and ouabain (a Na+/K+‐ATPase inhibitor) infusion on microdialysate glutamate and aspartate levels of CA3 hippocampal region were evaluated. Animals were assigned to one of the following groups: hypothyroid group (Hyp), receiving methimazole (anantithyroid drug); replacement group (Hyp + T4), receiving antithyroid treatment plus thyroxine; and euthyroid control group (Eut). Dialysate fractions were collected every 15 min to determine basal glutamate levels f... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5521730 Tue, 20 Dec 2011 05:00:00 +0100 5521730 http://www.medworm.com/index.php?rid=5521729&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22808 AbstractGonadal hormones regulate expression and activation of protein tau. Tibolone is a drug used as first‐ choice comprehensive treatment for the relief of menopausal symptoms, because it and its various metabolites have estrogenic properties and progestogenic/androgenic effects; however, the effect on the activation of tau protein and its signaling cascade in the brain is unknown. We studied the effect of chronic administration of estradiol (E2), progesterone (P4), and tibolone (TIB) on the expression and phosphorylation of microtubule‐associated protein tau and glycogen synthase kinase‐3β (GSK3β) in the hippocampus and cerebellum of ovariectomized rats. Ovariectomized adult female rats were implanted with pellets of vehicle, E2, or P4 or were treated with TIB by oral administr... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5521729 Tue, 20 Dec 2011 05:00:00 +0100 5521729 http://www.medworm.com/index.php?rid=5521728&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22776 AbstractThe role of hypoxia sensor proteins is important in responding and protecting cells against hypoxic/ischemic injury in brain. Seven in absentia homolog 1 (Siah1) regulates primarily the downstream sensor proteins factor inhibiting alpha subunit of hypoxia‐inducible factor‐1 (FIH) under normoxic conditions and prolyl hydroxylases domain 3 (PHD3) under hypoxic conditions. In the present study, we investigated the temporal and spatial changes of these hypoxia sensor proteins, Siah1, FIH, and PHD3, after 60 min of transient middle cerebral artery occlusion (tMCAO) up to 72 hr after reperfusion in ICR mice. Immunohistochemistry and Western blot analyses showed that Siah1 was quickly and strongly induced in neuronal cells of the ischemic penumbra, with a peak at 2 hr, and gradually r... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5521728 Tue, 20 Dec 2011 05:00:00 +0100 5521728 http://www.medworm.com/index.php?rid=5521727&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22792 AbstractIschemia elicits a variety of stress responses in neuronal cells, which result in cell death. wldS Mice bear a mutation that significantly delays Wallerian degeneration. This mutation also protects all neuronal cells against other types of stresses resulting in cell death, including ischemia. To clarify the types of stresses that neuronal cell bodies derived from wldS mice are protected from, we exposed primary cultured neurons derived from wldS mice to various components of hypoxic stress. We found that wldS mouse neurons are protected against cellular injury induced by reoxygenation following hypoxic stress. Furthermore, we found that wldS mouse neurons are protected against functional impairment of the mitochondrial electron transport chain. These data suggest that WldS protein ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5521727 Tue, 20 Dec 2011 05:00:00 +0100 5521727 http://www.medworm.com/index.php?rid=5521726&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22794 This study demonstrates that calpain 2 expression is required for the dispersal of glioblastoma cells within the dynamic microenvironment of the brain, identifying zebrafish as a valuable orthotopic system for studying glioblastoma cell invasion. © 2011 Wiley‐Liss, Inc. (Source: Journal of Neuroscience Research) Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5521726 Tue, 20 Dec 2011 05:00:00 +0100 5521726 http://www.medworm.com/index.php?rid=5521725&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22796 AbstractAlzheimer's disease (AD) is characterized by senile plaques caused by amyloid‐β peptide (Aβ) accumulation. It has been reported that Aβ generation and accumulation occur in membrane microdomains, called lipid rafts, which are enriched in cholesterol and glycosphingolipids. Moreover, the ablation of cholesterol metabolism has been implicated in AD. Neprilysin (NEP), a neutral endopeptidase, is one of the major Aβ‐degrading enzymes in the brain. Activation of NEP is a possible therapeutic target. However, it remains unknown whether the activity of NEP is regulated by its association with lipid rafts. Here we show that only the mature form of NEP, which has been glycosylated in the Golgi, exists in lipid rafts, where it is directly associated with phosphatidylserine. Moreover,... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5521725 Tue, 20 Dec 2011 05:00:00 +0100 5521725 http://www.medworm.com/index.php?rid=5521724&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22803 AbstractDiabetes and obesity are characterized by hyperlipidemia and represent risk factors for premature neurological disorders. Diabetic/obese animals have impaired adult neurogenesis. We hypothesize that lipotoxicity leading to neurogenesis impairment plays a role in the development of neurological complications. If so, normalizing neurogenesis in diabetes/obesity could be therapeutically useful in counteracting neurological dysfunction. The goal of this study was to determine the potential of pituitary adenylate cyclase‐activating polypeptide (PACAP) to protect adult neural stem cells (NSCs) from lipotoxicity and to study the expression of PACAP receptors in NSCs under lipotoxic conditions in vitro and in the subventricular zone in vivo. The viability of NSCs isolated from the adult ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5521724 Tue, 20 Dec 2011 05:00:00 +0100 5521724 http://www.medworm.com/index.php?rid=5438788&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22793 AbstractTo study the mechanisms of noise‐induced hearing loss and the phantom noise, or tinnitus, often associated with it, we used a mouse model of noise damage designed for reproducible and quantitative structural analyses. We selected the posteroventral cochlear nucleus, which has shown considerable plasticity in past studies, and correlated its changes with the distribution of neurotrophin 3 (NT3). We used volume change, optical density analysis, and microscopic cluster analysis to measure the degeneration after noise exposure. There was a fluctuation pattern in the reorganization of nerve terminals. The data suggest that the source and size of the nerve terminals affect their capacity for regeneration. We hypothesize that the deafferentation of ventral cochlear nucleus is the struct... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5438788 Thu, 24 Nov 2011 00:04:17 +0100 5438788 http://www.medworm.com/index.php?rid=5438791&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22790 AbstractAluminium is considered an environmental neurotoxicant and causes many neurological disorders, whereas zinc is vital for many biological functions. The present study was carried out to investigate the role of Zn, if any, in mitigating the adverse effects inflicted by Al on carbohydrate metabolism in rat brain. Male Sprague‐Dawley rats weighing 140–160 g were divided into four different groups: normal control, Al‐treated (100 mg/kg b.w./day in drinking water via oral gavage), Zn‐treated (227mg/liter in drinking water), and combined Al‐ and Zn‐treated rats. All the treatments were continued for 2 months, and their effects on carbohydrate‐metabolizing enzymes were studied. Additionally, expressions of the proteins glycogen synthase kinase‐3 (GSK3) and protein phosphata... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5438791 Wed, 23 Nov 2011 05:00:00 +0100 5438791 http://www.medworm.com/index.php?rid=5438790&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22791 In conclusion, we report for the first time evidence indicating that minocycline may inhibit PCD pathways that are additional to conventional apoptosis. © 2011 Wiley Periodicals, Inc. (Source: Journal of Neuroscience Research) Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5438790 Wed, 23 Nov 2011 05:00:00 +0100 5438790 http://www.medworm.com/index.php?rid=5438789&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22795 AbstractThe sorting nexins (SNXs) are a family of proteins functioning in diverse processes, including endocytosis, endosomal sorting, and endosomal signaling. Sorting nexin 12 (SNX12) is one of the SNXs family members; however, its function remains unknown. To clarify the function of SNX12, in this study, we first investigated the expression profiles in mice, particularly in the central nervous system (CNS), and then analyzed the functional role on neurite outgrowth. We found that SNX12 was widely expressed in the adult mouse CNS and that its expression level was higher in the cerebral cortex than in other examined regions. SNX12 expression was detected in the neurons but not the glial cells of the adult mouse cerebral cortex. In the fetal brain, SNX12 expression increased during the embr... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5438789 Wed, 23 Nov 2011 05:00:00 +0100 5438789 http://www.medworm.com/index.php?rid=5398257&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22786 AbstractSpinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder manifested by ataxia and seizure. SCA10 is caused by a large expansion of an intronic ATTCT pentanucleotide repeat in the ATXN10 gene. We have recently postulated a toxic RNA‐mediated gain of function in the pathogenesis of spinal cerebellar ataxia type 10 (SCA10). The spliced intron‐9 RNA containing the expanded AUUCU repeat aggregates in SCA10 cells and sequesters hnRNP K. hnRNP K sequestration triggers the translocation of protein kinase Cδ (PKCδ) to mitochondria, leading to activation of caspase‐3 and apoptosis. To confirm the toxic RNA‐mediated gain of function, we generated a new transgenic mouse model in which the expanded pentanucleotide repeats are constructed in the 3′�... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5398257 Sat, 12 Nov 2011 01:04:17 +0100 5398257 http://www.medworm.com/index.php?rid=5398258&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22800 AbstractCalpain, an intracellular cysteine protease, has been widely reported to be involved in neuronal cell death. The purpose of this study is to investigate the role of calpain activation in axonal damage‐induced retinal ganglion cell (RGC) death. Twelve‐week‐old male calpstatin (an endogenous calpain inhibitor) knockout mice (CAST KO) and wild‐type (WT) mice were used in this study. Axonal damage was induced by optic nerve crush (NC) or tubulin destruction induced by leaving a gelatin sponge soaked with vinblastine (VB), a microtubule disassembly chemical, around the optic nerve. Calpain activation was assessed by immunoblot analysis, which indirectly quantified the cleaved α‐fodrin, a substrate of calpain. RGCs were retrogradely labeled by injecting a fluorescent tracer, F... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5398258 Tue, 08 Nov 2011 05:00:00 +0100 5398258 http://www.medworm.com/index.php?rid=5378149&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22789 AbstractOlfactory mucosa is a source of cells for transplant‐mediated repair of spinal cord injury (SCI) and is currently being assessed in clinical trials. We previously reported that olfactory mucosa can generate two types of sphere‐forming cells with stem cell‐like properties. Here we have assessed the repair potential of these cells in a rodent SCI model. Sphere‐forming cells transplanted into a dorsal column injury integrated with the host spinal cord, filling the injury cavity, but showed no evidence of differentiation in vivo. Moreover, transplants supported robust axonal regeneration, particularly when suspensions of smaller spheres, rather than large aggregates, were transplanted. However, tract‐tracing of dorsal column fibers showed that regenerating axons did not exten... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5378149 Sat, 05 Nov 2011 20:33:47 +0100 5378149 http://www.medworm.com/index.php?rid=5378157&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22758 AbstractToll‐like receptor 3 (TLR3) recognizes double‐stranded RNA and induces type I interferon (IFN)‐mediated antiviral immunity against a number of viral infections. Type III IFN (IFN‐λ) is a newly identified antiviral cytokine that has biological functions similar to those of type I IFNs. We thus investigated the role of IFN‐λ in TLR3 activation‐mediated inhibition of herpes simplex virus type 1 (HSV‐1) in human primary astrocytes. Human astrocytes express endogenous IFN‐λ1 and IFN‐λ receptor complex, interleukin‐28 receptor α subunit (IL‐28Rα), and IL‐10Rβ. The activation of TLR3 by poly‐I:C treatment significantly induced the expression of IFN‐λ1 and IFN‐λ2/3 in astrocytes. The induction of IFN‐λ contributed to TLR3 activation‐mediated HSV�... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5378157 Fri, 04 Nov 2011 04:00:00 +0100 5378157 http://www.medworm.com/index.php?rid=5378156&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22780 Abstractβ‐Amyloid protein (Aβ) is thought to be responsible for neuronal apoptosis in Alzheimer's disease (AD). Paradoxically, Aβ can also promote neurogenesis, both in vitro and in vivo, by inducing neural progenitor cells (NPCs) to differentiate into neurons. However, the mechanisms of Aβ‐induced neurogenesis are unknown. Here we examined the role of DNA polymerase‐β (DNA pol‐β), a DNA repair enzyme that is required for proper neurogenesis during brain development and is also responsible for Aβ‐induced neuronal apoptosis. In neurospheres obtained from the adult mouse subventricular zone (SVZ), the knockdown of DNA pol‐β or its pharmacological blockade showed that the enzyme functioned both to repress proliferation of early nestin+ progenitor cells and to promote the m... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5378156 Fri, 04 Nov 2011 04:00:00 +0100 5378156 http://www.medworm.com/index.php?rid=5378154&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22783 AbstractThe complex process of microglial activation encompasses several functional activation states associated either with neurotoxic/antineurogenic or with neurotrophic/proneurogenic properties, depending mainly on the extent of activation and the nature of the activating stimuli. Several studies have demonstrated that acute exposure to the prototypical activating agent lipopolysaccharide (LPS) confers antineurogenic properties upon microglial cells. Acutely activated microglia ortheir conditioned media (CM) reduce neural stem progenitor cell (NPC) survival and prevent NPC differentiation into neurons. The present study tested the hypothesis that docosahexaenoic acid (DHA), a long‐chain polyunsatured fatty acid (L‐PUFA) with potent immunomodulatory properties, could dampen microglia... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5378154 Fri, 04 Nov 2011 04:00:00 +0100 5378154 http://www.medworm.com/index.php?rid=5378153&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22755 In this study, MOMCs and macrophages were prepared from rat peripheral blood and transplanted intracranially into the ischemic core of syngeneic rats that had undergone a left middle cerebral artery occlusion procedure. Neurological deficits, as evaluated by the corner test, were less severe in the MOMC‐transplanted rats than in macrophage‐transplanted or mock‐treated rats. Histological evaluations revealed that the number of microvessels that had formed in the ischemic boundary area by 4 weeks after transplantation was significantly greater in the MOMC‐transplanted rats than in the control groups. The blood vessel formation was preceded by the appearance of round CD31+ cells, which we confirmed were derived from the transplanted MOMCs. Small numbers of bloodvessels incorporating M... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5378153 Fri, 04 Nov 2011 04:00:00 +0100 5378153 http://www.medworm.com/index.php?rid=5378152&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22777 This study provides the first example of the CHOP‐mediated cell death that is independent of the UPR. © 2011 Wiley Periodicals, Inc. (Source: Journal of Neuroscience Research) Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5378152 Fri, 04 Nov 2011 04:00:00 +0100 5378152 http://www.medworm.com/index.php?rid=5378151&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22787 AbstractZinc is an endogenous N‐methyl‐D‐aspartate (NMDA) receptor blocker. It is possible that zinc‐mediated modification of hippocampal CA1 long‐term potentiation (LTP) is linked to the expression of NMDA receptor subunits, which varies with postnatal development. In the present study, the effect of ZnCl2 and CaEDTA, a membrane‐impermeable zinc chelator, on CA1 LTP induction was examined in hippocampal slices from immature (3‐week‐old) and young (6‐week‐old) rats. Tetanus (10–100 Hz, 1 sec)‐induced CA1 LTP was more greatly enhanced in 3‐week‐old rats. CA1 LTP was inhibited in the presence of 2‐amino‐5‐phosphonovalerate (APV), an NMDA receptor antagonist, and CaEDTA in 3‐week‐old rats, as in the case of 6‐week‐old rats reported previously. In 3‐... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5378151 Fri, 04 Nov 2011 04:00:00 +0100 5378151 http://www.medworm.com/index.php?rid=5378150&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22788 This study demonstrates a critical role of minocycline (a potent inhibitor of microglial activation)‐modulated BDNF in the induction and maintenance of behavioral hypersensitivity in a rat model of CIBP. We assessed mechanical threshold and spontaneous pain of CIBP rats. Moreover, minocycline was administered intrathecally from day 4 to day 6 (early stage) or from day 10 to day 12 (later stage), after carcinoma cell inoculation. Real‐time PCR, Western blots, and double immunofluorescence were used to detect the expression of OX‐42 (marker of activated microglia), phosphorylated p38‐MAPK (p‐p38), and BDNF. We found that intrathecal minocycline could prevent CIBP at an early stage of tumor growth (from day 4 to day 6). However, at the late stage (from day 10 to day 12), intrathecal... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5378150 Fri, 04 Nov 2011 04:00:00 +0100 5378150 http://www.medworm.com/index.php?rid=5378158&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22756 In this study, mice were subjected to 20 min of global brain ischemia and sacrificed 72 hr later. Berberine was administered for 7 days prior to ischemia and daily until sacrifice. Mice treated with berberine showed reduced matrix metalloproteinase‐9 (MMP‐9) activity. Berberine inhibited gelatinase activity directly in in situ zymography and reduced neuronal damage following global ischemia. Laminin expression and NeuN expression were markedly reduced in CA1 and CA2 areas after ischemia, and berberine reduced the laminin degradation and neuronal loss. In the TUNEL assay, damaged neurons were also apparent in the CA1 and CA2 areas, and berberine reduced TUNEL‐positive cells. These data demonstrate that berberine, a plant alkaloid, may protect from hippocampal neuronal damage following... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5378158 Thu, 03 Nov 2011 04:00:00 +0100 5378158 http://www.medworm.com/index.php?rid=5378161&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22779 AbstractA secreted protein, lipocalin‐2 (LCN2), has been previously shown to regulate a variety of cellular phenotypes such as cell death, migration, and morphology. The role of LCN2, however, appears to be different depending on the cellular context. Here, we investigated how LCN2 influences neuronal phenotypes by using primary cortical neuronal cell cultures and neuroblastoma cell lines as a model. When exposed to LCN2 protein, neurons and neuroblastoma cells were sensitized to cell death evoked by nitric oxide, oxidative stress, and tumor necrosis factor‐α (TNF‐α). A forced expression of lcn2 in glia enhanced neuronal cell death in cocultures of glia and neurons, indicating that both exogenous protein addition and endogenous expression of lcn2 give rise to similar results. Iron ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5378161 Sun, 30 Oct 2011 04:00:00 +0100 5378161 http://www.medworm.com/index.php?rid=5378160&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22781 AbstractOrexinergic neurons are discretely localized within the lateral hypothalamus and have widespread projections to the whole brain. Here, the role of orexin/hypocretin‐2 receptors (OX2) in modulating extracellular concentrations of neurotransmitters was evaluated in the hypothalamus and the prefrontal cortex (PFC) of OX2 knockout (KO) mice by using a microdialysis technique. In the hypothalamus, basal concentrations of norephinephrine (NE), acetylcholine (ACh), and histamine (Hist) were significantly higher in KO mice, whereas KCl perfusion (147 mM) resulted in significantly lesser increases in NE, ACh, and Hist release in KO compared with wild‐type (WT) mice. No differences in basal concentrations or evoked release of serotonin (5‐HT) or dopamine (DA) were found in the hypothal... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5378160 Sun, 30 Oct 2011 04:00:00 +0100 5378160 http://www.medworm.com/index.php?rid=5378159&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22784 AbstractCNS injury is often localized but can be followed by more widespread secondary degenerative events that usually result in greater functional loss. Using a partial transection model in rat optic nerve (ON). we recently demonstrated in vivo increases in the oxidative stress‐associated enzyme MnSOD 5 min after injury. However, mechanisms by which early oxidative stress spreads remain unclear. In the present study, we assessed ion distributions, additional oxidative stress indicators, and ion channel immunoreactivity in ON in the first 24 hr after partial transection. Using nanoscale secondary ion mass spectroscopy (NanoSIMS), we demonstrate changes in the distribution pattern of Ca ions following partial ON transection. Regions of elevated Ca ions in normal ON in vivo rapidly decrea... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5378159 Sun, 30 Oct 2011 04:00:00 +0100 5378159 http://www.medworm.com/index.php?rid=5356854&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22751 AbstractHypoxia/ischemia induces proliferation of neural progenitor cells (NPCs) in rodent and human brain; however, the mechanisms remain unknown. We investigated the effects of metabotropic glutamate receptor 5 (mGluR5) on NPC proliferation under hypoxia, the expression of cyclin D1, and the activation of the mitogen‐activated protein kinases (MAPKs) signaling pathway in cell culture. The results showed that hypoxia induced mGluR5 expression on NPCs in vitro. Under hypoxia, the mGluR5 agonists DHPG and CHPG significantly increased NPC proliferation in cell activity, diameter of neurospheres, bromodeoxyuridine (BrdU) incorporation and cell division, and expression of cyclin D1, with decreasing cell death. The mGluR5 siRNA and antagonist MPEP decreased the NPC proliferation and expressio... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5356854 Fri, 28 Oct 2011 19:17:26 +0100 5356854 http://www.medworm.com/index.php?rid=5332733&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22774 AbstractThe hippocampus and the striatum have traditionally been considered as part of different and independent memory systems. However, there is evidence that supports a functional interaction between the hippocampus and the dorsal striatum at least in particular learning tasks. Here, we evaluated the functional contribution of both brain regions in a visual discrimination learning task using cytochrome c oxidase (CO) quantitative histochemistry. Compared with other brain metabolic mapping techniques, CO activity reflects steady‐state neuronal energy demand. Rats were trained for 6 days in a water T‐maze to find a hidden escape platform associated with an intramaze visual cue. A control group of animals swam for an equivalent amount of time compared as the trained group but without a... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5332733 Fri, 21 Oct 2011 02:59:24 +0100 5332733 http://www.medworm.com/index.php?rid=5332734&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22773 AbstractMutations in the CLN6 gene cause a variant form of late infantile neuronal ceroid lipofuscinosis, a relentless neurodegenerative disease that is inherited as an autosomal recessive trait in humans and in the naturally occurring nclf mouse strain. The CLN6 protein is localized in the endoplasmic reticulum, but it has an unknown function. To develop a molecular understanding of neurodegeneration induced by mutations in CLN6, we examined the spatial and temporal distribution of Cln6 mRNA expression in murine brain. By using Northern blot and tissue qPCR array techniques, a single Cln6 transcript was detected throughout the adult brain, with greatest expression in the cerebellum and hypothalamus. Real‐time qPCR showed 2.4–4‐fold increases in Cln6 mRNA levels in the cortex and cer... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5332734 Wed, 19 Oct 2011 04:00:00 +0100 5332734 http://www.medworm.com/index.php?rid=5332736&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22745 AbstractIt has been shown that ouabain (OUA) can activate the Na,K‐ATPase complex and mediate intracellular signaling in the central nervous system (CNS). Inflammatory stimulus increases glutamatergic transmission, especially at N‐methyl‐D‐aspartate (NMDA) receptors, which are usually coupled to the activation of nitric oxide synthase (NOS). Nuclear factor‐κB (NF‐κB) activation modulates the expression of genes involved in development, plasticity, and inflammation. The present work investigated the effects of OUA on NF‐κB binding activity in rat hippocampus and the influence of this OUA‐Na,K‐ATPase signaling cascade in NMDA‐mediated NF‐κB activation. The findings presented here are the first report indicating that intrahippocampal administration of OUA, in a conce... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5332736 Tue, 18 Oct 2011 04:00:00 +0100 5332736 http://www.medworm.com/index.php?rid=5332735&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22772 AbstractTransient global brain ischemia causes delayed neuronal death in the hippocampus that has been associated with impairments in hippocampus‐dependent brain function, such as mood, learning, and memory. We investigated the expression of voltage‐dependent Kcnh1 and Kcnh5, ether à go‐go‐related Eag1 and Eag2 (KV10.1 and KV10.2), and small‐conductance calcium‐activated SK3 (KCa2.3, Kcnn3) K+ channels in the hippocampus in rats after transient global brain ischemia. We tested whether the expression of these channels is associated with behavioral changes by evaluating the animals in the elevated plus maze and step‐down inhibitory avoidance task. Seven or tweny‐eight days after transient global brain ischemia, one group of rats had the hippocampus bilaterally dissected, and... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5332735 Tue, 18 Oct 2011 04:00:00 +0100 5332735 http://www.medworm.com/index.php?rid=5332739&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22765 In this study, we examined the consequences of oxygen level on the viability and metabolism of primary cultures of cortical neurons. Our results indicate that physiological oxygen level (5% O2) has a beneficial effect on cortical neuronal survival and mitochondrial function in vitro. Moreover, oxygen level affects metabolic fluxes: glucose uptake and glycolysis was enhanced at physiological oxygen level, whereas glucose oxidation and fatty acid oxidation were reduced. Adenosine monophosphate‐activated protein kinase (AMPK) was more activated in 5% O2 and appears to play a role in these metabolic effects. Inhibiting AMPK activity with compound C decreased glucose uptake, intracellular ATP level, and viability in neurons cultured in 5% O2. These data indicate that oxygen level is an import... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5332739 Mon, 17 Oct 2011 04:00:00 +0100 5332739 http://www.medworm.com/index.php?rid=5332738&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22771 AbstractImmunization with neurally derived peptides (INDP) boosts the action of an autoreactive immune response that has been shown to induce neuroprotection in several neurodegenerative diseases, especially after spinal cord (SC) injury. This strategy provides an environment that promotes neuronal survival and tissue preservation. The mechanisms by which this autoreactive response exerts its protective effects is not totally understood at the moment. A recent study showed that INDP reduces lipid peroxidation. Lipid peroxidation is a neurodegenerative phenomenon caused by the increased production of reactive nitrogen species such as nitric oxide (NO). It is possible that INDP could be interfering with NO production. To test this hypothesis, we examined the effect of INDP on the amount of N... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5332738 Mon, 17 Oct 2011 04:00:00 +0100 5332738 http://www.medworm.com/index.php?rid=5332737&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22775 In conclusion, our work for the first time demonstrates the neuroprotective effect of HupA on synaptic deficits in APPswe/PS1dE9 transgenic mice and further clarifies the potential pharmacological targets for this protective effect, in which modulation of nonamyloidogenic and amyloidogenic APP processing pathways may be both involved. These findings may provide adequate evidence for the clinical and experimental benefits gained from HupA treatment. © 2011 Wiley‐Liss, Inc. (Source: Journal of Neuroscience Research) Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5332737 Mon, 17 Oct 2011 04:00:00 +0100 5332737 http://www.medworm.com/index.php?rid=5282795&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22747 AbstractUsing stem cells to replace lost neurons is a promising strategy for treating retinal neurodegenerative diseases. Among their multiple functions, Müller glial cells are retina stem cells, with a robust regenerative potential in lower vertebrates, which is much more restricted in mammals. In rodents, most retina progenitors exit the cell cycle immediately after birth, differentiate as neurons, and then cannot reenter the cell cycle. Here we demonstrate that, in mixed cultures with Müller glial cells, rat retina progenitor cells expressed stem cell properties, maintained their proliferative potential, and were able to preserve these properties and remain mitotically active after several consecutive passages. Notably, these progenitors retained the capacity to differentiate as photo... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5282795 Wed, 05 Oct 2011 01:05:43 +0100 5282795 http://www.medworm.com/index.php?rid=5282802&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22742 AbstractAspirin and its main metabolite salicylate are widely used to relieve pain, treat inflammatory diseases, and prevent ischemic stroke. Multiple pathways are responsible for the therapeutic actions exerted by these drugs. One of the pathways is targeting neuronal receptors/ion channels in the central nervous system. Correspondingly, increasing evidence has implicated acid‐sensing ion channels (ASICs) in the processes of the diseases that are medicated by aspirin and salicylate. We therefore employed whole‐cell patch‐clamp recordings to examine the effects of salicylate as well as aspirin on ASICs in cultured cortical neurons of the rat. We recorded rapid and reversible inhibition of ASIC current by millimolar concentrations of aspirin and salicylate and found that salicylate re... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5282802 Tue, 04 Oct 2011 04:00:00 +0100 5282802 http://www.medworm.com/index.php?rid=5282801&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22770 AbstractNeuropeptide Y (NPY) exerts anxiolytic‐ and antidepressant‐like effects in rodents that appear to be mediated via Y1 receptors. Gene therapy using recombinant viral vectors to induce overexpression of NPY in the hippocampus or amygdala has previously been shown to confer anxiolytic‐like effect in rodents. The present study explored an alternative and more specific approach: overexpression of Y1 receptors. Using a recombinant adeno‐associated viral vector (rAAV) encoding the Y1 gene (rAAV‐Y1), we, for the first time, induced overexpression of functional transgene Y1 receptors in the hippocampus of adult mice and tested the animals in anxiety‐ and depression‐like behavior. Hippocampal Y1 receptors have been suggested to mediate seizure‐promoting effect, so the effects... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5282801 Tue, 04 Oct 2011 04:00:00 +0100 5282801 http://www.medworm.com/index.php?rid=5282800&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22764 AbstractGap junctions are specialized transmembrane channels that allow rapid electrical signalling and direct intercellular communication for maintenance and coordination of normal cellular activities and homeostasis. Although gap junction channels in the nervous system mediate intercellular coupling between glial cells and between neurons, they also contribute to the spread of secondary damage and inflammation under pathological conditions. There is now evidence of the involvement of gap junctions in chronic pain caused by nervous system damage or tissue inflammation. In this Mini‐Review, we highlight recent studies demonstrating the dynamic plasticity of gap junctions in response to nervous system injury and the effects of gap junction blockade on neuronal survival and modulation of p... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5282800 Tue, 04 Oct 2011 04:00:00 +0100 5282800 http://www.medworm.com/index.php?rid=5282799&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22767 In this study we have addressed the question of whether functional TLRs are expressed on oligodendrocytes, the myelinating cells of the central nervous system. Primary cultures of rat oligodendrocytes at different maturation stages were found to express TLR2 and, to lesser extent, TLR3. Immunocytochemical analysis revealed that both TLRs were localized at the cell body and primary processes and were excluded from myelin‐like membranes. Interestingly, innate immune receptor ligands were able to modulate oligodendrocyte survival, differentiation, and myelin‐like membrane formation, indicating that TLRs on oligodendrocytes are functional. In highly purified oligodendrocytes cultures, the TLR2 agonist zymosan promoted survival, differentiation, and myelin‐like membrane formation, whereas... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5282799 Tue, 04 Oct 2011 04:00:00 +0100 5282799 http://www.medworm.com/index.php?rid=5282798&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22763 AbstractThe neuronal ceroid lipofuscinoses (NCLs) are a family of devastating pediatric neurodegenerative disorders and currently represent the most common form of pediatric‐onset neurodegeneration. Infantile NCL (INCL), the most aggressive of these disorders, is caused by mutations in the CLN1 gene that encodes the enzyme palmitoyl protein thioesterase 1 (PPT1). Previous studies have suggested that glutamatergic neurotransmission may be disrupted in INCL, so the present study investigates glutamate receptor function in the Ppt1−/− mouse model of INCL by comparing the sensitivity of cultured wild‐type (WT) and Ppt1−/− cerebellar granule cells to glutamate receptor‐mediated toxicity. Ppt1−/− neurons were significantly less sensitive to AMPA receptor‐mediated toxicity but... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5282798 Tue, 04 Oct 2011 04:00:00 +0100 5282798 http://www.medworm.com/index.php?rid=5282797&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22754 AbstractReactive oxygen species (ROS) are key players in ischemia‐induced neurodegeneration. We investigated whether hippocampal neurons may lack sufficient redox‐buffering capacity to protect against ROS attacks. Using organotypic hippocampal slice cultures (OHSCs) transiently exposed to oxygen and glucose deprivation (OGD) and gerbils suffering from a two‐vessel occlusion (2VO) as complementary ex vivo and in vivo models, we have elucidated whether the intrinsic redox systems interfere with ischemia‐induced neurodegeneration. Cell‐ type‐specific immunohistological staining of hippocampal slice cultures revealed that pyramidal neurons, in contrast to astrocytes and microglia, express free thiols only weakly. In addition, free thiol levels were extensively decreased throughout ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5282797 Tue, 04 Oct 2011 04:00:00 +0100 5282797 http://www.medworm.com/index.php?rid=5282796&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22750 AbstractMorphine is frequently used as an analgesic and sedative in preterm infants. Adult rats exposed to morphine have an altered hippocampal neurochemical profile and decreased neurogenesis in the dentate gyrus of the hippocampus. To evaluate whether neonatal rats are similarly affected, rat pups were injected twice daily with 2 mg/kg morphine or normal saline from postnatal days 3 to 7. On postnatal day 8, the hippocampal neurochemical profile was determined using in vivo 1H NMR spectroscopy. The mRNA and protein concentrations of specific analytes were measured in hippocampus, and cell division in dentate gyrus was assessed using bromodeoxyuridine. The concentrations of γ‐aminobutyric acid (GABA), taurine, and myo‐insotol were decreased, whereas concentrations of glutathione, pho... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5282796 Tue, 04 Oct 2011 04:00:00 +0100 5282796 http://www.medworm.com/index.php?rid=5282803&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22743 AbstractCholesterol synthesis and transport in oligodendrocytes are essential for optimal myelination and remyelination in pathological conditions such as multiple sclerosis. However, little is known about cholesterol homeostasis in the myelin‐forming oligodendrocytes. Liver X receptors (LXRs) are nuclear oxysterol receptors that regulate genes involved in cholesterol homeostasis and may therefore play an important role in de‐ and remyelination. We investigated whether LXRs regulate cholesterol homeostasis in oligodendrocytes. mRNA expression of genes encoding LXR‐α and LXR‐β and their target genes (ABCA1, ABCG1, ABCG4, apoE, and LDLR) was detected in oligodendrocytes derived from both neonatal and adult rats using quantitative real‐time PCR. The expression of LXR‐β and seve... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5282803 Mon, 03 Oct 2011 04:00:00 +0100 5282803 http://www.medworm.com/index.php?rid=5270928&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22761 AbstractThe extracellular matrix surrounds different neuronal compartments in the mature nervous system. In a variety of vertebrates, most brain regions are loaded with a distinct type of extracellular matrix around the somatodendritic part of neurons, termed perineuronal nets. The present study reports that chondrotin sulfate proteoglycan‐based matrix is structured differently in the human lateral geniculate body. Using various chondrotin sulfate proteoglycan‐based extracellular matrix antibodies, we show that perisomatic matrix labeling is rather weak or absent, whereas dendrites are contacted by axonal coats appearing as small, oval structures. Confocal laser scanning microscopy and electron microscopy demonstrated that these typical structures are associated with synaptic loci on d... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5270928 Sun, 02 Oct 2011 03:07:28 +0100 5270928 http://www.medworm.com/index.php?rid=5258237&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22766 In this study we have established a paradigm of hypoxic preconditioning based on a chick embryo model of normobaric acute hypoxia previously developed by our group. With this model, we analyzed the role of hypoxia‐inducible factor‐1α (HIF‐1α) stabilization during preconditioning in HIF‐1 signaling after the hypoxic injury and in the development of a neuroprotective effect against the insult. To this end, we used a pharmacological approach, based on the in vivo administration of positive (Fe2+, ascorbate) and negative (CoCl2) modulators of the activity of HIF‐prolyl hydroxylases (PHDs), the main regulators of HIF‐1. We have found that preconditioning has a reinforcing effect on HIF‐1 accumulation during the subsequent hypoxic injury. In addition, we have also demonstrated th... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5258237 Tue, 27 Sep 2011 18:16:37 +0100 5258237 http://www.medworm.com/index.php?rid=5247649&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22744 We examined the effects of citalopram on delayed rectifier outward K+ current (IK) in mouse cortical neurons. Extracellular citalopram reversibly inhibited IK in a dose‐dependent manner and significantly shifted both steady‐state activation and inactivation curves toward hyperpolarization. Neither 5‐HT itself nor antagonists of 5‐HT and dopamine receptors could abolish citalopram‐induced inhibition of IK. In addition, intracellular application of GTPγ‐S similarly failed to prevent the inhibition of IK by citalopram. When applied intracellularly, citalopram had no effect on IK and did not influence the reduction of IK induced by extracellular citalopram. The effect of citalopram was use dependent, but not frequency dependent, and it did not require channel opening. Electrophysi... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5247649 Sat, 24 Sep 2011 00:31:41 +0100 5247649 http://www.medworm.com/index.php?rid=5247654&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22757 AbstractThe developing human brain shows rapid myelination and axonal changes during childhood, adolescence, and early adulthood, requiring successive evaluations to determine normative values for potential pathological assessment. Fiber characteristics can be examined by axial and radial diffusivity procedures, which measure water diffusion parallel and perpendicular to axons and show primarily axonal status and myelin changes, respectively. Such measures are lacking from widespread sites for the developing brain. Diffusion tensor imaging data were acquired from 30 healthy subjects (age 17.7 ± 4.6 years, range 8–24 years, body mass index 21.5 ± 4.5 kg/m2, 18 males) using a 3.0‐Tesla MRI scanner. Diffusion tensors were calculated, principal eigenvalues determined, and axial and radia... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5247654 Wed, 21 Sep 2011 04:00:00 +0100 5247654 http://www.medworm.com/index.php?rid=5247653&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22759 In conclusion, our data demonstrate that sildenafil produces a significant, long‐lasting neuroprotective effect against MDMA‐induced 5‐HT deficits. This effect is apparently mediated by an increased expression of MnSOD and a subsequent reduced susceptibility to the oxidative stress caused by MDMA. © 2011 Wiley‐Liss, Inc. (Source: Journal of Neuroscience Research) Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5247653 Wed, 21 Sep 2011 04:00:00 +0100 5247653 http://www.medworm.com/index.php?rid=5247652&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22760 In this study, we decreased the expression of NMDAR in the NTS using gene transfer to target receptor subunits and evaluate long‐term effects. Seven days after the injection of lentiviral vectors containing the NR1a subunit cDNA of NMDAR, in antisense orientation, into the intermediate NTS of Wistar rats, BP was measured, and the formalin test of nociception was performed. The antisense vector induced a decrease of NR1 expression in the NTS and elicited BP rises and hypoalgesia. Antisense vectors inhibited formalin‐evoked c‐Fos expression in the spinal cord, indicating decreased nociceptive activity of spinal neurons. Using a time‐course approach, we verified that the onset of both the increases in BP and the hypoalgesia was at 4 days after vector injection into the NTS. The inject... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5247652 Wed, 21 Sep 2011 04:00:00 +0100 5247652 http://www.medworm.com/index.php?rid=5247651&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22762 AbstractCreatine (Cr) is a very popular ergogenic molecule that has recently been shown to have antioxidant properties. The effectiveness of Cr supplementation in treating neurological diseases and Cr deficiency syndromes has been demonstrated, and experimental reports suggest that it plays an important role in CNS development. In spite of this body of evidence, the role of Cr in functional and structural neuronal differentiation is still poorly understood. Here we used electrophysiological, morphological, and biochemical approaches to study the effects of Cr supplementation on in vitro differentiation of spinal neuroblasts under standard conditions or subjected to oxidative stress, a status closely related to perinatal hypoxia‐ischemia, a severe condition for developing brain. Cr supple... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5247651 Wed, 21 Sep 2011 04:00:00 +0100 5247651 http://www.medworm.com/index.php?rid=5247650&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22769 AbstractThe aim of this study was to develop a sensitive and rapid blood marker to detect ischemic brain injury, because imaging techniques have a limited capacity to identify lesions during the first crucial hours without massive tissue destruction. Rats were subjected to middle cerebral artery occlusion for various durations (0.5–3 hr), followed by reperfusion. At different time points after ischemia and/or ischemia‐reperfusion, the amounts of glial fibrillary acidic protein (GFAP) and microtubule‐associated protein 2 (MAP2) in the cerebrospinal fluid (CSF) and serum were analyzed by Western blotting. Brain infarction was observed in an ischemia‐duration‐dependent manner. GFAP was drastically increased in the CSF 24 and 48 hr after reperfusion, without change in the serum level... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5247650 Wed, 21 Sep 2011 04:00:00 +0100 5247650 http://www.medworm.com/index.php?rid=5235350&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22753 This study sought to determine whether Cbl was capable of reducing behavioral and neuronal alterations in nVHL rats. The behavioral analysis included locomotor activity induced by novel environment and amphetamine, social interaction, and sensoriomotor gating. The morphological evaluation included dendritic analysis by using the Golgi‐Cox procedure and stereology to quantify the total cell number in PFC and NAcc. Behavioral data show a reduction in the hyperresponsiveness to novel environment‐ and amphetamine‐induced locomotion, with an increase in the total time spent in social interactions and in prepulse inhibition in Cbl‐treated nVHL rats. In addition, neuropathological analysis of the limbic regions also showed amelioration of dendritic retraction and spine loss in Cbl‐treat... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235350 Tue, 20 Sep 2011 19:45:36 +0100 5235350 http://www.medworm.com/index.php?rid=5235356&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22717 This report suggests that patterned neuronal activity could repress delayed progression of white matter injury and promote CNS repair in neurological conditions that involve white matter damage. Journal of Neuroscience Research (2011) © 2011 Wiley‐Liss, Inc. (Source: Journal of Neuroscience Research) Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235356 Mon, 19 Sep 2011 04:00:00 +0100 5235356 http://www.medworm.com/index.php?rid=5235355&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22736 AbstractRecent research in neural development has highlighted the importance of markers to discriminate phenotypic alterations of neural cells at various developmental stages. We isolated a new monoclonal antibody, 4F2, which was shown to be specific for an oligodendrocyte lineage. In primary cultures of oligodendroglial and mixed neural cells, the 4F2 antibody labeled a large proportion of Sox2+, Sox10+, A2B5+, NG2+, Olig2+, O4+, and myelin basic protein (MBP)+ cells but did not label any GFAP+ or NeuN+ cells. In immunohistochemisty of rat embryos, the 4F2 antibody labeled a portion of neuroepithelial cells of the neural tube at embryonic day 9. The 4F2‐positive cells were located initially in the ventricular zone as Musashi1+ Tuj1− populations and distributed throughout the striatum;... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235355 Mon, 19 Sep 2011 04:00:00 +0100 5235355 http://www.medworm.com/index.php?rid=5235354&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22740 AbstractEndocytosis of the synaptic vesicle is a complicated process, in which many proteins and lipids participate. Phosphatidylinositol 4,5‐bisphosphate (PIP2) plays important roles in the process, and the dynamic regulation of this lipid is one of the key events. Synaptojanin is a PIP2 phosphatase, and dephosphorylation of PIP2 of the clathrin coated‐vesicle results in the uncoating of the vesicle. NAP‐22 is one of the major proteins of the neuronal detergent‐resistant membrane microdomain and localizes in both the presynaptic plasma membrane and the synaptic vesicle. To elucidate the role of NAP‐22 in synaptic function, a screening of the NAP‐22 binding proteins through pull‐down assay was performed. In addition to CapZ protein, synaptojanin‐1 was detected by LC‐MS/MS... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235354 Mon, 19 Sep 2011 04:00:00 +0100 5235354 http://www.medworm.com/index.php?rid=5235353&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22748 AbstractInflammation accompanied by severe oxidative stress plays a vital role in the orchestration and progression of neurodegeneration prevalent in chronic and acute central nervous system pathologies as well as in aging. The proinflammatory cytokine tumor necrosis factor‐α (TNFα) elicits the formation of the bioactive ceramide by stimulating the hydrolysis of the membrane lipid sphingomyelin by sphingomyelinase activities. Ceramide stimulates the formation of reactive oxygen species (ROS) and apoptotic mechanisms in both neurons and nonneuronal cells, establishing a link between sphingolipid metabolism and oxidative stress. We demonstrated in SH‐SY5Y human neuroblastoma cells and primary cortical neurons that TNFα is a potent stimulator of Mg2+‐dependent neutral sphingomyelinas... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235353 Mon, 19 Sep 2011 04:00:00 +0100 5235353 http://www.medworm.com/index.php?rid=5235352&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22749 AbstractIonotropic glutamate receptors, especially the α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) receptor subtype, undergo dynamic trafficking between the surface membrane and intracellular organelles. This trafficking activity determines the efficacy and strength of excitatory synapses and is subject to modulation by changing synaptic inputs. Given the possibility that glutamate receptors in the central nervous system might be a sensitive target of anesthetic agents, this study investigated the possible impact of anesthesia on trafficking and subcellular expression of AMPA receptors in adult mouse brain neurons in vivo. We found that anesthesia induced by a systemic injection of pentobarbital did not alter total protein levels of three AMPA receptor subuni... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235352 Mon, 19 Sep 2011 04:00:00 +0100 5235352 http://www.medworm.com/index.php?rid=5235351&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22752 AbstractPhenotypic differences in Schwann cells (SCs) may help to guide axonal regeneration down motor or sensory specific pathways following peripheral nerve injury. The goal of this study was to identify phenotypic markers for SCs harvested from the cutaneous (sensory) and quadriceps (motor) branches of the rat femoral nerve and to study the effects of expansion culture on the expression patterns of these motor or sensory phenotypic markers. RNA was extracted from SCs harvested from the motor and sensory branches of the rat femoral nerve and analyzed using Affymetrix Gene Chips (Rat Genome 230 v2.0 Array A). Genes that were upregulated in motor SCs compared with the sensory SCs or vice versa were identified, and the results were verified for a subset of genes using quantitative real‐ti... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235351 Mon, 19 Sep 2011 04:00:00 +0100 5235351 http://www.medworm.com/index.php?rid=5235357&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22727 AbstractN‐myc downstream‐regulated gene 2 (Ndrg2) has been associated with cell proliferation, differentiation, and apoptosis. Ndrg2 expression in the brain is induced by glucocorticoid treatment or chronic stress in vivo. It has been postulated that glucocorticoid‐induced Ndrg2 expression in astrocytes is regulated by the glucocorticoid response element half‐site (GRE1/2) upstream of the Ndrg2 transcription site. Here we examined the mechanisms of dexamethasone‐induced Ndrg2 expression in rat astrocytes. Ndrg2 mRNA expression in primary astrocytes was significantly increased after 24 hr of exposure to dexamethasone in a concentration‐dependent manner. Dexamethasone‐induced Ndrg2 mRNA and protein expression was blocked by pretreatment with RU486, a glucocorticoid receptor ant... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235357 Fri, 16 Sep 2011 04:00:00 +0100 5235357 http://www.medworm.com/index.php?rid=5220553&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22729 AbstractParkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNC). Most epidemiologic studies have demonstrated that PD has a higher prevalence in males than in females. Both hormones and genetic factors have been considered to be contributors to this phenomenon. In the present study, we used primary cultures of ventral mesencephalic (VM) neurons from E13.5 Balb/C mice to investigate whether there were any gender differences in gene expression and cell sensitivity to oxidative stress in sex segregated cultures. We also investigated the role of SRY, the sex‐determining region on the Y chromosome, and the female hormone estrogen in the gender dimorphism. We measured the expression levels o... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5220553 Thu, 15 Sep 2011 15:31:16 +0100 5220553 http://www.medworm.com/index.php?rid=5235367&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22701 AbstractGene expression regulation is essential for correct functioning of the cell. Complex processes such as development, apoptosis, cell differentiation, and cell cycling require a fine tuning of gene expression. MicroRNAs (miRNAs) are small RNAs that have been recognized as key components of the gene expression regulatory machinery. By sequence complementarity, miRNAs recognize target mRNAs and inhibit their function through degradation or by repressing their translation. The development of the central nervous system (CNS) requires precise and exquisitely regulated gene expression patterns. It is now widely recognized that miRNAs have the capacity to provide such fine regulation both in time and in space. High‐throughput analyses as well as classical molecular biology approaches have... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235367 Thu, 15 Sep 2011 04:00:00 +0100 5235367 http://www.medworm.com/index.php?rid=5235366&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22735 AbstractBecause of controversy about the role of the p75 neurotrophin receptor (p75NTR) in the cholinergic basal forebrain (CBF), we investigated this region in p75NTR third exon knockout mice that were congenic with 129/Sv controls. They express a shortened intracellular form of p75NTR, permitting detection of p75NTR‐expressing cells. We performed separate counts of choline acetyltransferase (ChAT)‐expressing and p75NTR‐expressing neurons. In agreement with past reports, the number of ChAT‐immunoreactive neurons in knockout mice was greater than in wild‐type mice, and this was evident in each of the main anatomical divisions of the CBF. In contrast, the number of p75NTR‐immunoreactive neurons did not differ between genotypes. The biggest increase in ChAT neurons (27%) was in t... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235366 Thu, 15 Sep 2011 04:00:00 +0100 5235366 http://www.medworm.com/index.php?rid=5235365&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22715 In this study, we investigated the gelatinolytic activity in young adult (3‐month‐old) and aged (1‐year‐old) mice subjected to photothrombotic stroke. Using in situ zymography and gel zymography, we found that the basal gelatinolytic activity in the intact cerebral cortex was similar at both investigated ages. Similarly, after photothrombosis, the increased gelatinolytic response up to 7 days poststroke was the same in young and aged brains. At both ages, early activation of gelatinolysis in the ischemic core and the perilesional area was present in neuronal nuclei as revealed by colocalization of gelatinolytic product with NeuN immunostaining and DAPI. Additionally, application of specific antibodies against MMP‐9 and MMP‐2 revealed the increase in MMP‐9 immunoreactivity in ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235365 Thu, 15 Sep 2011 04:00:00 +0100 5235365 http://www.medworm.com/index.php?rid=5235364&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22721 AbstractDuring immune‐mediated demyelinating lesions, the endocannabinoid system is involved in the pathogenesis of both neuroinflammation and neurodegeneration through different mechanisms. Here we explored the cellular distribution of the CB1 receptor (CB1R) in the central nervous system (CNS) and detected the level of CB1R expression during experimental autoimmune encephalomyelitis (EAE) by RT‐qPCR, Western blotting, and immunostaining. Expression of CB1R was observed in neurons and microglia/macrophages but was barely detected in astrocytes. During EAE, the expression of CB1R in spinal cords was reduced at days 9, 17, and 28 postimmunization (p.i.), but the level of CB1R expression in spleens did not show a significant difference compared with complete Freund's adjuvant (CFA)‐imm... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235364 Thu, 15 Sep 2011 04:00:00 +0100 5235364 http://www.medworm.com/index.php?rid=5235363&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22730 AbstractThe central histaminergic nervous system, originating from the tuberomammillary nucleus of the hypothalamus, widely innervates almost the whole brain as well as the spinal cord. However, the effect of histamine on spinal motoneurons, the final common path for motor control, is still unknown. By using 8–14‐day‐old rat spinal slice preparations and intracellular recordings, the effect of histamine on motoneurons in lumbar spinal cord and the underlying mechanisms were studied. Bath application of histamine (30–300 μM) induced a membrane depolarization in the majority of recorded spinal motoneurons (78/90, 86%). Perfusing slices with tetrodotoxin or low‐Ca2+/high‐Mg2+ medium did not block the histamine‐induced excitation, indicating a direct postsynaptic action of hista... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235363 Thu, 15 Sep 2011 04:00:00 +0100 5235363 http://www.medworm.com/index.php?rid=5235362&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22731 Abstractβ Amyloid, present in senile plaques, has been related largely to neuronal loss in the brain of patients with Alzheimer's disease. However, how neurons respond to β amyloid insults is still poorly understood. Here we show that β amyloid increases somatostatin and cortistatin gene expression mainly through an increase in histone 3 lysine 4 methylation (H3K4me3), a modification associated with transcriptional activation. Somatostatin and cortistatin partially decreased β amyloid toxicity in primary cortical neurons in culture. Thus we suggest that neurons respond to β amyloid insults by releasing somatostatin and cortistatin, which will act as a protective agent against β amyloid toxicity. Our results suggest a relevant function for both neuropeptides against β amyloid toxicit... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235362 Thu, 15 Sep 2011 04:00:00 +0100 5235362 http://www.medworm.com/index.php?rid=5235361&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22734 AbstractInflammation and oxidative stress play major roles in the pathogenesis after spinal cord injury (SCI). Here, we examined the neuroprotective effects of Angelica dahuricae radix (ADR) extract after SCI. ADR extract significantly decreased the levels of proinflammatory factors such as tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), inducible nitric oxide synthase (iNOS), and cyclooxygenase‐2 (COX‐2) in a lipopolysaccharide (LPS)‐activated microglial cell line, BV2 cells. ADR extract also significantly alleviated the level of reactive oxygen species in LPS‐activated BV2 cells. To examine the neuroprotective effect of ADR extract after SCI, spinally injured rats were administered ADR extract orally at a dose of 100 mg/kg for 14 day... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235361 Thu, 15 Sep 2011 04:00:00 +0100 5235361 http://www.medworm.com/index.php?rid=5235360&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22732 AbstractNeuronal degeneration and aberrant neovascularization are common problems of ischemic retinopathies. Pigment epithelium‐derived factor (PEDF), a neuroprotective protein and an inhibitor of angiogenesis, is produced by retinal glial (Müller) cells and can counterbalance elevated levels of vascular endothelial growth factor (VEGF), the expression of which is regulated primarily by hypoxia‐inducible factor (HIF)‐1. In an approach to mimic transient ischemia in vitro, primary Müller cells were cultured under transient and strong hypoxia (0.2% O2), followed by reoxygenation at 2.5% O2, and molecular mechanisms that might contribute to changes in the intraretinal PEDF level were determined. Hypoxic conditions caused an increasing expression of HIF‐1α and led to upregulation of... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235360 Thu, 15 Sep 2011 04:00:00 +0100 5235360 http://www.medworm.com/index.php?rid=5235359&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22741 In conclusion, overexpression of IL‐10 by using NLSCt transfection vector did not synergistically neuroprotect the excitotoxically damaged postnatal rat brain but induced changes in the astroglial and microglial and inflammatory cell response. © 2011 Wiley‐Liss, Inc. (Source: Journal of Neuroscience Research) Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235359 Thu, 15 Sep 2011 04:00:00 +0100 5235359 http://www.medworm.com/index.php?rid=5235358&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22737 AbstractMale and female rodents respond differently to acute stress. We tested our hypothesis that this sex difference is based on differences in stress sensitivity of forebrain areas, by determining possible effects of a single acute psychogenic stressor (1‐hr restraint stress) on neuronal gene expression (c‐Fos and FosB immunoreactivities), storage of corticotropin‐releasing factor (CRF) immunoreactivity, and CRF production (CRF mRNA in situ hybridization) as well as the expression of genes associated with epigenetic processes (quantitative RT‐PCR) in the rat paraventricular nucleus (PVN), the oval and fusiform subdivisions of the bed nucleus of the stria terminalis (BSTov and BSTfu, respectively), and the central amygdala (CeA), in both males and females. Compared with females, ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5235358 Thu, 15 Sep 2011 04:00:00 +0100 5235358 http://www.medworm.com/index.php?rid=5220555&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22746 AbstractGlutamatergic neurotransmission accounts for a considerable part of energy consumption related to signaling in the brain. Chemical energy is provided by adenosine triphosphate (ATP) formed in glycolysis and tricarboxylic acid (TCA) cycle combined with oxidative phosphorylation. It is not clear whether ATP generated in these pathways is equivalent in relation to fueling of the energy‐requiring processes, i.e., vesicle filling, transport, and enzymatic processing in the glutamatergic tripartite synapse (the astrocyte and pre‐ and postsynapse). The role of astrocytic glycogenolysis in maintaining theses processes also has not been fully elucidated. Cultured astrocytes and neurons were utilized to monitor these processes related to glutamatergic neurotransmission. Inhibitors of gly... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5220555 Wed, 14 Sep 2011 04:00:00 +0100 5220555 http://www.medworm.com/index.php?rid=5220554&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22728 AbstractThe morphology of sciatic nerves from leptin‐deficient ob/ob mice and leptin receptor‐deficient db/db mice, both models for obesity, peripheral diabetic neuropathy, and the metabolic syndrome, has yet to be examined for changes in nerve fibers and in endoneural microvessels. Sciatic nerves from three groups of 4‐month‐old mice (WT C57BL6, ob/ob, and db/db) were investigated. In ultrathin sections, the thickness of myelin sheaths was significantly reduced in small, medium‐sized, and large axons of db/db mice compared with WT mice. In ob/ob mice, only large fibers showed a decrease in myelin sheath thickness. The number of nonmyelinated nerve fibers was lower in ob/ob mice than in the db/db group. A thickened basal lamina of Schwann cells occurred in the ob/ob group only. I... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5220554 Wed, 14 Sep 2011 04:00:00 +0100 5220554 http://www.medworm.com/index.php?rid=5205495&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22768 AbstractThe process of neurogenesis continues throughout life, with thousands of new neurons generated every day in the mammalian brain. Impairment of hippocampal neurogenesis has been suggested to be involved in neurodegenerative conditions, including the cognitive decline associated with aging, Alzheimer's disease, Parkinson's disease, and ionizing radiation. These neurodegenerative conditions are all characterized by proinflammatory changes and increased numbers of activated microglia. Activated microglia produce a variety of proinflammatory factors, including interleukin‐6, tumor necrosis factor‐α, reactive oxygen species, and nitric oxide, all of which are antineurogenic. These same factors have also been shown to suppress mitochondrial function, but the role of mitochondria in n... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5205495 Sun, 11 Sep 2011 07:55:32 +0100 5205495 http://www.medworm.com/index.php?rid=5205497&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22782 (Source: Journal of Neuroscience Research) Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5205497 Fri, 09 Sep 2011 04:00:00 +0100 5205497 http://www.medworm.com/index.php?rid=5205496&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22738 This study has extended these observations and, by using a combination of 2D‐PAGE/Western blotting and immunogold electron microscopy, determined that these different conformations are exhibited in vivo and arise from differential phosphorylation of GLUT‐1 and not from alternative splicing or altered O‐ or N‐linked glycosylation. © 2011 Wiley‐Liss, Inc. (Source: Journal of Neuroscience Research) Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5205496 Fri, 09 Sep 2011 04:00:00 +0100 5205496 http://www.medworm.com/index.php?rid=5180990&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22733 AbstractThe developmentally regulated myelin basic proteins (MBPs), which arise from the golli (gene of oligodendrocyte lineage) complex, are highly positively charged, intrinsically disordered, multifunctional proteins having several alternatively spliced isoforms and posttranslational modifications, and they play key roles in myelin compaction. The classic 18.5‐kDa MBP isoform has a proline‐rich region comprising amino acids 92–99 (murine sequence –T92PRTPPPS99–) that contains a minimal SH3 ligand domain. We have previously shown that 18.5‐kDa MBP binds to several SH3 domains, including that of Fyn, a member of the Src family of tyrosine kinases involved in a number of signaling pathways during CNS development. To determine the physiological role of this binding as well as th... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5180990 Fri, 02 Sep 2011 12:39:30 +0100 5180990 http://www.medworm.com/index.php?rid=5107157&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22710 AbstractGlutamate transport represents a key mechanism for maintaining low level of glutamate in the extracellular milieu to restrict the excitotoxic action of glutamate released during ischemia/reperfusion (I/R) injury. Recently, it has been reported that glutamate transporter‐1 (GLT‐1) is a novel target for peroxisome proliferator‐activated receptor‐γ (PPARγ) agonist, which shows neuroprotection following oxygen glucose deprivation (OGD) in neuronal–astrocytic cocultures. Hence, the present study was undertaken to investigate the role of rosiglitazone in neuroprotection mediated by GLT‐1 following focal cerebral I/R injury in rat. We found that rosiglitazone (2 mg/kg i.p) administered pre‐ or post‐I/R injury significantly improved behavioral outcome and decreased cerebr... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5107157 Tue, 09 Aug 2011 14:19:55 +0100 5107157 http://www.medworm.com/index.php?rid=5107160&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22720 This study investigates the regulation of P‐gp in an in vitro model of gp120‐triggered human fetal astrocytes (HFAs). In this system, elevated levels of interleukin‐6 (IL‐6), IL‐1β, and tumor necrosis factor‐α were detected in culture supernatants. Pretreatment with CCR5 neutralizing antibody attenuated cytokine secretion, suggesting that gp120‐CCR5 interaction mediated cytokine production. Treatment with gp120 (R5‐tropic) resulted in reduced P‐gp expression (64%) and function as determined by increased (1.6‐fold) cellular accumulation of [3H]digoxin, a P‐gp substrate. Exposure to R5 or R5/X4‐tropic viral isolates led to a downregulation in P‐gp expression (75% or 90%, respectively), and treatment with IL‐6 also showed lower P‐gp expression (50%). Moreover, ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5107160 Sun, 07 Aug 2011 23:00:00 +0100 5107160 http://www.medworm.com/index.php?rid=5107159&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22725 AbstractThe mammalian nicotinamide‐adenine dinucleotide (NAD)‐dependent deacetylase Sirt1 impacts different processes involved in the maintenance of brain integrity and in the pathogenic pathways associated with several neurodegenerative disorders, including Alzheimer's disease. Here we used human Sirt1 transgenic mice to demonstrate that neuron‐specific Sirt1 overexpression promoted neurite outgrowth and improved cell viability under normal and nutrient‐limiting conditions in primary culture systems and that Sirt1‐overexpressing neurons exhibited higher tolerance to cell death or degeneration induced by amyloid‐β1–42 oligomers. Coincidentally, we found that enhanced Sirt1 expression in neurons downregulated the mammalian target of rapamycin (mTOR) protein levels and its pho... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5107159 Sun, 07 Aug 2011 23:00:00 +0100 5107159 http://www.medworm.com/index.php?rid=5107158&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22723 AbstractAlterations in glycogen synthase kinase‐3β (GSK3β) and protein phosphatase‐2A (PP2A) have been proposed to be involved in the abnormal tau phosphorylation and aggregation linked to Alzheimer's disease (AD). Interconnections between GSK3β and PP2A signaling pathways are well established. Targeting tau kinases was proposed to represent a therapeutic strategy for AD. However, which tau kinases should be blocked and to what extent, keeping in mind that kinases have physiological roles? Because most kinase inhibitors are relatively specific and many of them interfere with the cell cycle, it is necessary to develop more specific tau kinase inhibitors devoid of cell toxicity. Here, we used the PP2A inhibition by okadaic acid (OKA) in primary cultured cortical neurons as an in vitro... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5107158 Sun, 07 Aug 2011 23:00:00 +0100 5107158 http://www.medworm.com/index.php?rid=5095360&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22711 AbstractThe activation of microglia and astrocytes in the spinal cord is involved in the progress of cancer pain. Propentofylline (PPF), a glial modulating agent, alleviates pain hypersensitivity in neuropathic pain models. The present study investigated the potential roles of PPF in a preclinical rat model of bone caner pain established by inoculating Walker 256 cells into the left tibia. At day 9 postinoculation, single administration of PPF (10 μg/10 μl, i.t.) significantly but transiently suppressed mechanical allodynia induced by bone cancer. Repeated application of PPF (10 μg/10 μl, i.t., once daily from days 9 to 12) persistently relieved mechanical allodynia on the side ipsilateral to surgery. Immunohistochemistry and ELISA showed that microglia and astrocytes in the spinal cor... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5095360 Fri, 05 Aug 2011 10:56:56 +0100 5095360 http://www.medworm.com/index.php?rid=5095361&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22722 AbstractThe biology of cerebral white matter injury has been woefully understudied, in part because of the difficulty of reliably modeling this type of injury in rodents. Periventricular leukomalacia (PVL) is the predominant form of brain injury and the most common cause of cerebral palsy in premature infants. PVL is characterized by predominant white matter injury. No specific therapy for PVL is presently available, because the pathogenesis is not well understood. Here we report that two types of mouse PVL models have been created by hypoxia‐ischemia with or without systemic coadministration of lipopolysaccharide (LPS). LPS coadministration exacerbated hypoxic‐ischemic white matter injury and led to enhanced microglial activation and astrogliosis. Drug trials with the antiinflammatory... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5095361 Mon, 01 Aug 2011 23:00:00 +0100 5095361 http://www.medworm.com/index.php?rid=5077355&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22690 AbstractRB4CD12 is a phage display antibody that recognizes a heparan sulfate (HS) glycosaminoglycan epitope. The epitope structure is proposed to contain a trisulfated disaccharide, [–IdoA(2‐OSO3)‐GlcNSO3(6‐OSO3)–], which supports HS binding to various macromolecules such as growth factors and cytokines in central nervous tissues. Chemically modified heparins that lack the trisulfated disaccharides failed to inhibit the RB4CD12 recognition of HS chains. To determine the localization of the RB4CD12 anti‐HS epitope in the brain, we performed an immunohistochemical analysis for cryocut sections of mouse brain. The RB4CD12 staining signals were colocalized with laminin and were detected abundantly in the vascular basement membrane. Bacterial heparinases eliminated the RB4CD12 stai... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5077355 Sat, 30 Jul 2011 06:07:10 +0100 5077355 http://www.medworm.com/index.php?rid=5077358&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22691 AbstractEndoplasmic reticulum (ER) stress and oxidative stress are involved in many diseases, including retinal disorders, causing toxicity in various tissues and cells; however, intracellular signaling of ER stress and cross‐talk between ER stress and oxidative stress are unknown in retinal ganglion cells (RGC), whose degeneration is associated with glaucoma. The aim of the study was to clarify the mechanisms of ER stress‐ and oxidative stress‐induced RGC death, using cultured retinal ganglion cells (RGC‐5) in vitro and N‐methyl‐D‐aspartate (NMDA)‐ or ER stress‐induced retinal damage in mice in vivo. We focused on both BH3‐interacting domain death agonist (Bid) and caspase‐2, which work as apoptosis promotion factors. In an in vitro study, both Bid and caspase‐2 in... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5077358 Thu, 28 Jul 2011 23:00:00 +0100 5077358 http://www.medworm.com/index.php?rid=5077357&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22724 AbstractIn this experiment, sensitivity to female facial attractiveness was examined by comparing event‐related potentials (ERPs) in response to attractive and unattractive female faces within a study‐test paradigm. Fourteen heterosexual participants (age range 18–24 years, mean age 21.67 years) were required to judge 84 attractive and 84 unattractive face images as either “attractive” or “unattractive.” They were then asked whether they had previously viewed each face in a recognition task in which 50% of the images were novel. Analyses indicated that attractive faces elicited more enhanced ERP amplitudes than did unattractive faces in judgment (N300 and P350–550 msec) and recognition (P160 and N250–400 msec and P400–700 msec) tasks on anterior locations. Moreover, lon... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5077357 Thu, 28 Jul 2011 23:00:00 +0100 5077357 http://www.medworm.com/index.php?rid=5077356&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22726 AbstractThe hypothalamo–neurohypophyseal system displays significant plasticity when subjected to physiological stimuli, such as dehydration, parturition, or lactation. This plasticity arises at the neurochemical and electrophysiological levels but also at a structural level. Several studies have demonstrated the role of monoaminergic afferents in controlling neurochemical and electrophysiological plasticity of the supraoptic nucleus (SON) and of the neurohypophysis (NH), but little is known about how the changes in structural plasticity are triggered. We used Tg8 mice, disrupted for the monoamine oxidase A gene, to study monamine involvement in the architecture of the SON and of the NH. SON astrocytes in Tg8 mice displayed an active status, characterized by an increase in S100β express... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5077356 Thu, 28 Jul 2011 23:00:00 +0100 5077356 http://www.medworm.com/index.php?rid=5077364&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22671 In conclusion, these findings demonstrate that, in addition to showing promising antidiabetic properties, MA has a direct beneficial effect in cerebral ischemic injury, which may be correlated with the promotion of glutamate clearance by NF‐κB‐mediated GLT‐1 up‐regulation. © 2011 Wiley‐Liss, Inc. (Source: Journal of Neuroscience Research) Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5077364 Wed, 27 Jul 2011 23:00:00 +0100 5077364 http://www.medworm.com/index.php?rid=5077363&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22643 (Source: Journal of Neuroscience Research) Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5077363 Wed, 27 Jul 2011 23:00:00 +0100 5077363 http://www.medworm.com/index.php?rid=5077362&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22680 AbstractNeurogenesis within the adult brain is restricted to selected areas, one of which is the dentate gyrus (DG). Several growth factors have been reported to affect neurogenesis in the adult DG. However, a role of fibroblast growth factor‐2 (FGF‐2) in adult hippocampal neurogenesis has not been firmly established. We have analyzed neurogenesis in the DG using in vivo and in vitro approaches. FGF‐2–/– mice revealed no alterations in the number of proliferating cells but a significant decrease in the numbers of newly generated neurons. Moreover, FGF‐2 added to hippocampal slice cultures from FGF‐2–/– mice was unable to rescue the phenotype. Although an increase in death of neurogenic cells in the FGF‐2‐deficient DG could not be specifically demonstrated, there was a... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5077362 Wed, 27 Jul 2011 23:00:00 +0100 5077362 http://www.medworm.com/index.php?rid=5077361&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22713 AbstractMaxi‐K+ (BK) channel diversity is attributed to alternative splicing in the kcnma1 gene. The resultant variants manifest themselves in different cell types, tissues, and functions, such as excitation, metabolism, and signaling. Immunoelectron microscopy revealed immunogold particle labeling of BK in apical and basal regions of inner and outer hair cells, respectively. Additional labeling occurs in Deiters' cells and the inner mitochondrial membrane. Identification of full‐length sequences reveals 27 BK variants from embryonic and postnatal mouse inner ear, per classification by tail motif, VYR, DEC, and ERL, and by exon usage. Three predicted start codons are found encoding MAN, MSS, and MDA, of which MDA shows the greatest expression through all stages in development, whereas ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5077361 Wed, 27 Jul 2011 23:00:00 +0100 5077361 http://www.medworm.com/index.php?rid=5077360&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22714 AbstractZinc ion elevation contributes to acute excitotoxic brain injury and correlates with the severity of dementia in chronic neurodegenerative diseases. Downstream control of zinc‐triggered signals is believed to be an efficient countermeasure. In the current study, we examined whether the flavonoid luteolin (Lu) could protect human neuroblastoma SH‐SY5Y cells against zinc toxicity. We found that Lu suppressed overproduction of reactive oxygen species and protected against apoptotic cell death induced by zinc. By using specific inhibitors, we found that zinc strongly triggered Akt and ERK1/2 activation via a PI3K–Akt–NF‐κB–ERK1/2‐dependent pathway. Furthermore, Lu completely blocked this activation. Our study strongly supports the hypothesis that Lu might protect SH‐SY... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5077360 Wed, 27 Jul 2011 23:00:00 +0100 5077360 http://www.medworm.com/index.php?rid=5077359&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22719 AbstractCalcium influx via N‐methyl‐D‐aspartate (NMDA)‐subtype glutamate receptors (NMDARs) regulates the intracellular trafficking of NMDARs, leading to long‐lasting modification of NMDAR‐mediated synaptic transmission that is involved in development, learning, and synaptic plasticity. The present study investigated the contribution of such NMDAR‐dependent synaptic trafficking in spinal dorsal horn to the induction of pain hypersensitivity. Our data showed that direct activation of NMDARs by intrathecal NMDA application elicited pronounced mechanical allodynia in intact mice, which was concurrent with a specific increase in the abundance of NMDAR subunits NR1 and NR2B at the postsynaptic density (PSD)‐enriched fraction. Selective inhibition of NR2B‐containing NMDARs (NR2... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5077359 Wed, 27 Jul 2011 23:00:00 +0100 5077359 http://www.medworm.com/index.php?rid=5061901&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22696 In this study, we tested the hypothesis that decreased number and impaired function of circulating EPCs correlate with CA formation in patients. Blood circulating EPCs were identified by flow cytometry. The level of plasma vascular endothelial growth factor (VEGF) was measured by ELISA. Circulating EPCs from patients (n = 27) were cultured in vitro, and the function of EPCs was evaluated by cell migration and senescence‐associated β‐galactosidase activity. The number of circulating EPCs was significantly decreased in both unruptured and ruptured CA patients compared with healthy control subjects. Impaired migratory capacity and elevated cellular senescence of cultured EPCs were observed in patients with CA (ruptured and unruptured). The percentages of EPC senescence in patients with C... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5061901 Mon, 25 Jul 2011 21:53:24 +0100 5061901 http://www.medworm.com/index.php?rid=5061904&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22712 In conclusion, the results demonstrate that the effects of Cerebrolysin persist for a significant period of time following treatment termination and suggest that this prolonged effect may involve the neurotrophic factor‐like activity of Cerebrolysin. © 2011 Wiley‐Liss, Inc. (Source: Journal of Neuroscience Research) Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5061904 Sun, 24 Jul 2011 23:00:00 +0100 5061904 http://www.medworm.com/index.php?rid=5061903&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22716 AbstractMultiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Exogenous cell replacement in MS lesions has been proposed as a means of achieving remyelination when endogenous remyelination has failed. However, the ability of exogenous cells to remyelinate axons in the presence of inflammation remains uncertain. We have explored the remyelinating capacity of an oligodendrocyte progenitor cell line CG‐4 transduced with the GFP gene and transplanted adjacent to a zymosan‐induced focal demyelination model in the rat spinal cord. The resulting zymosan‐induced lesions were characterized by persistent macrophage/microglia activation, focal demyelination, degeneration of axons, and reactive astrogliosis. GFP+ CG‐4 cells were found to migrate prefer... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5061903 Sun, 24 Jul 2011 23:00:00 +0100 5061903 http://www.medworm.com/index.php?rid=5061902&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22718 AbstractEstradiol attenuates the ATP‐induced increase of intracellular calcium concentration ([Ca2+]i) in rat dorsal root ganglion (DRG) neurons by blocking the L‐type voltage gated calcium channel (VGCC). Because ATP is a putative nociceptive signal, this action may indicate a site of estradiol regulation of pain. In other neurons, 17β‐estradiol (E2) has been shown to modulate L‐type VGCC through a membrane estrogen receptor‐group II metabotropic glutamate receptor (mGluR2/3). The present study investigated whether the rapid estradiol attenuation of the ATP‐induced increase in [Ca2+]i requires mGluR2/3. Previously we showed that DRG (L1–S3) express ERα, P2X3, and mGluR2/3 receptors. DRG were acutely dissociated by enzyme digestion and grown in short‐term culture for imag... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5061902 Sun, 24 Jul 2011 23:00:00 +0100 5061902 http://www.medworm.com/index.php?rid=5018877&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22699 AbstractCurrent behavioral measurements for motor impairment are not consistently sensitive in rodent models of partial nigrostriatal dopamine (DA) depletion. In addition to exploratory and somatosensory behavior, motor skills that are thought to be directly translatable to human Parkinson's disease patients are assessed. However, many of these motor tests require the training and learning of particular tasks, so it cannot be determined whether impairments are due to motor or to learning deficit. Therefore, we have quantified multiple temporal and spatial indices of gait dynamics in a model of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced partial nigrostriatal lesioning using a treadmill apparatus requiring no prior training. Three days following the cessation of ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5018877 Wed, 13 Jul 2011 00:36:39 +0100 5018877 http://www.medworm.com/index.php?rid=5018882&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22709 This study tested the hypothesis that sensitivity to the Ca2+‐induced loss of mitochondrial membrane potential (ΔΨm) and the sensitivity of the loss of ΔΨ to mitochondrial permeability transition pore (PTP) inhibitors are different for neurons and astrocytes. Primary cultures of rat cortical neurons and astrocytes were exposed to the Ca2+ ionophore 4‐Br‐A23187, and ΔΨm was monitored with the fluorescent probe tetramethylrhodamine methyl ester (TMRM). Ca2+ ionophore caused a decline in ΔΨm in both cell types that was partially inhibited by cyclosporin A (CsA) in astrocytes but not in neurons. Another PTP inhibitor, 2‐aminoethoxy‐diphenylborate, was ineffective at protecting against mitochondrial depolarization, but depolarization was inhibited by FK506, an immunosuppressan... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5018882 Sun, 10 Jul 2011 23:00:00 +0100 5018882 http://www.medworm.com/index.php?rid=5018881&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22702 We report here elevated EPO mRNA levels and protein release in cultured astrocytes following hypoxic stimulation by quantitative RT‐PCR and ELISA. Furthermore, the EPOR gene expressions were detected in cultured OPCs as in astrocytes and microglias by quantitative RT‐PCR. Cell staining revealed the EPOR expression in OPC. To evaluate the protective effect of endogenous EPO from astrocyte to OPCs, EPO/EPOR signaling was blocked by EPO siRNA or EPOR siRNA gene silencing in in vitro study. The suppression of endogenous EPO production in astrocytes by EPO siRNA decreased the protection to OPCs against hypoxic stress. Furthermore, OPC with EPOR siRNA had less cell survival after hypoxic/reoxygenation injury. This suggested that EPO/EPOR signaling from astrocyte to OPC could prevent OPC dama... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5018881 Sun, 10 Jul 2011 23:00:00 +0100 5018881 http://www.medworm.com/index.php?rid=5018880&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22708 AbstractHepatic encephalopathy (HE) is the major neurological complication occurring in patients with acute and chronic liver failure. Elevated levels of blood and brain ammonia are characteristic of HE, and astrocytes are the primary target of ammonia toxicity. In addition to ammonia, recent studies suggest that inflammation and associated cytokines (CKs) also contribute to the pathogenesis of HE. It was previously established that ammonia induces the mitochondrial permeability transition (mPT) in cultured astrocytes. As CKs have been shown to cause mitochondrial dysfunction in other conditions, we examined whether CKs induce the mPT in cultured astrocytes. Cultures treated with tumor necrosis factor‐α, interleukin‐1β, interleukin‐6, and interferon‐γ, individually or in a mixtu... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5018880 Sun, 10 Jul 2011 23:00:00 +0100 5018880 http://www.medworm.com/index.php?rid=5018879&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22706 AbstractSeveral studies have shown the protective and/or deleterious effects of dietary enrichment of single fatty acids (FAs) in several animal and cell‐culture models of Alzheimer's disease (AD). However, potential interactions among dietary fatty acids are traditionally ignored. None of these studies has examined and compared the differential effects of FAs in combination, as well as alone, for their effects on amyloid β production or AD. Here we investigated the effects of omega‐9 (oleic acid) and omega‐6 (linoleic and arachidonic acids) fatty acids, either alone or combined, on Aβ production by APP‐695 and SP‐C99 transfected COS‐7 cells. Overall, our results are the first to demonstrate that mixtures of FAs alter the production of Aβ40 and Aβ42 peptides and consequentl... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5018879 Sun, 10 Jul 2011 23:00:00 +0100 5018879 http://www.medworm.com/index.php?rid=5018878&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22707 AbstractMany inflammatory processes involve cAMP. Pharmacological manipulation of cAMP levels using specific phosphodiesterase (PDE) inhibitors provokes an antiinflammatory response. The aim of this study was to investigate changes in the pattern and levels of expression of mRNAs coding for the cAMP‐specific PDE4 family and subfamilies in mouse brain during the immediate acute immune response provoked by an intraperitoneal injection of lipopolysaccharide (LPS). PDE4B, and furthermore the splice variants PDE4B2 and PDE4B3, were the only mRNAs that showed altered expression. Whereas PDE4B2 presented increased expression at both 3 and 8 hr postinjection, PDE4B3 mRNA showed decreased expression that reached a minimum 8 hr postinjection. PDE4B2 mRNA upregulation was observed mainly in endothe... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5018878 Sun, 10 Jul 2011 23:00:00 +0100 5018878 http://www.medworm.com/index.php?rid=5007663&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22705 AbstractNumerous studies have implicated low levels of signaling in the Akt network with psychotic illnesses, and a growing body of literature has shown that all classes of antipsychotic drugs increase Akt signaling. The most clinically effective antipsychotic drug is clozapine. With Caenorhabditis elegans as a model system, this study demonstrates that clozapine is unique among antipsychotic drugs because it requires β‐arrestin and serum and glucocorticoid‐inducible kinase (SGK) in addition to Akt to suppress the nuclear localization of DAF‐16 (Forkhead box O [FOXO]). Lithium, a mood stabilizer often used to treat psychosis, also requires β‐arrestin and SGK to suppress the nuclear localization of DAF‐16. © 2011 Wiley‐Liss, Inc. (Source: Journal of Neuroscience Research) Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5007663 Fri, 08 Jul 2011 16:21:29 +0100 5007663 http://www.medworm.com/index.php?rid=5007665&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22704 The objective of the current study was to examine further whether maternal immune challenge has an influence on the cellular–biological features of the cortical progenitors that generate distinct cortical neuronal subtypes. We found the following abnormalities in the cortex of mice given the prenatal Poly I:C injection during later stages of cortical neurogenesis. First, proliferative activity and the expression of Pax6, which is a master regulator of the gene expression of transcription factors, were significantly decreased in the cortical progenitors. Second, the laminar allocation and gene expression were significantly altered in the daughter neurons generated at the same birth dates. These results demonstrate that specific abnormalities in the cortical progenitors preceded deficits i... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5007665 Mon, 04 Jul 2011 23:00:00 +0100 5007665 http://www.medworm.com/index.php?rid=5007664&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22703 AbstractGlycogen is the reservoir for glucose in the brain. Beyond the general agreement that glycogen serves as an energy source in the central nervous system, its exact role in brain energy metabolism has yet to be elucidated. Experiments performed in cell and tissue culture and animals have shown that glycogen content is affected by several factors, including glucose, insulin, neurotransmitters, and neuronal activation. The study of in vivo glycogen metabolism has been hindered by the inability to measure glycogen noninvasively, but, in the past several years, the development of a noninvasive localized 13C nuclear magnetic resonance (NMR) spectroscopy method has allowed the study of glycogen metabolism in the conscious human. With this technique, 13C‐glucose is administered intravenou... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=5007664 Mon, 04 Jul 2011 23:00:00 +0100 5007664 http://www.medworm.com/index.php?rid=4968148&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22700 In this study, we examined the potential cytoprotective effect of lithium in preventing oxidative stress‐induced protein accumulation and neuronal cell death in the presence of increased α‐synuclein levels in vitro and in vivo. Specifically, lithium administration was found to protect against cell death in a hydrogen peroxide‐treated, stable α‐synuclein‐enhanced green fluorescent protein (EGFP)‐overexpressing dopaminergic N27 cell line. Lithium feeding (0.255% lithium chloride) of 9‐month‐old pan‐neuronal α‐synuclein transgenic mice over a 3‐month period was also sufficient to prevent accumulation of oxidized/nitrated α‐synuclein as a consequence of chronic paraquat/maneb administration in multiple brain regions, including the glomerular layer, mitral cells, and... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4968148 Sun, 26 Jun 2011 19:40:20 +0100 4968148 http://www.medworm.com/index.php?rid=4968149&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22698 AbstractThalidomide, an inhibitor of tumor necrosis factor‐α (TNF‐α) production, has been indicated to be useful for many inflammatory and oncogenic diseases. In the present study, we examined whether thalidomide (50 mg/kg/day, p.o.) has a protective effect against N‐methyl‐D‐aspartate (NMDA)‐induced retinal neurotoxicity in rats. A morphometric analysis showed that systemic administration of thalidomide protects neural cells in the ganglion cell layer (GCL) in a dose‐dependent manner and significantly decreases the number of terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling (TUNEL)‐positive cells in GCL and in the inner nuclear layer (INL). ELISA showed that thalidomide significantly suppressed the elevation of TNF‐α 6 and 24 hr after an NMDA i... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4968149 Wed, 22 Jun 2011 23:00:00 +0100 4968149 http://www.medworm.com/index.php?rid=4944781&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22695 AbstractAny mutations in the human neural cell adhesion molecule L1 (hL1CAM) gene might cause various types of serious neurological syndromes in humans, characterized by increased mortality, mental retardation, and various malformations of the nervous system. Such missense mutations often cause severe abnormalities or even fatalities, and the reason for this may be a disruption of the adhesive function of L1CAM resulting from a misdirection of the degradative pathway. Transfection studies using neuroblastoma N2a cells demonstrated that hL1CAM carrying the missense mutations in the fibronectin‐like type III (FnIII) domains most likely is located within the endoplasmic reticulum (ER), but it is less well expressed on the cell surface. One mutant, L935P, in the fourth FnIII domain, was chos... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4944781 Sun, 19 Jun 2011 11:45:16 +0100 4944781 http://www.medworm.com/index.php?rid=4933502&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22620 AbstractHigh‐resolution immunohistochemistry shows that the receptor protein p75NTR is present in the nerve terminal, muscle cell, and glial Schwann cell at the neuromuscular junction (NMJ) of postnatal rats (P4–P6) during the synapse elimination period. Blocking the receptor with the antibody anti‐p75‐192‐IgG (1–5 μg/ml, 1 hr) results in reduced endplate potentials (EPPs) in mono‐ and polyinnervated synapses ex vivo, but the mean number of functional inputs per NMJ does not change for as long as 3 hr. Incubation with exogenous brain‐derived neurotrophic factor (BDNF) for 1 hr (50 nM) resulted in a significant increase in the size of the EPPs in all nerve terminals, and preincubation with anti‐p75‐192‐IgG prevented this potentiation. Long exposure (24 hr) in vivo of ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4933502 Fri, 17 Jun 2011 01:37:27 +0100 4933502 http://www.medworm.com/index.php?rid=4944785&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22684 AbstractDuring early vertebrate forebrain development, pioneer axons establish a symmetrical scaffold descending longitudinally through the rostral forebrain, thus forming the tract of the postoptic commissure (TPOC). In mouse embryos, this tract begins to appear at embryonic day 9.5 (E9.5) as a bundle of axons tightly constrained at a specific dorsoventral level. We have characterized the participation of the Slit chemorepellants and their Robo receptors in the control of TPOC axon projection. In E9.5–E11.5 mouse embryos, Robo1 and Robo2 are expressed in the nucleus origin of the TPOC (nTPOC), and Slit expression domains flank the TPOC trajectory. These findings suggested that these proteins are important factors in the dorsoventral positioning of the TPOC axons. Consistently with this ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4944785 Thu, 16 Jun 2011 23:00:00 +0100 4944785 http://www.medworm.com/index.php?rid=4944784&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22693 AbstractEndoplasmic reticulum (ER) stress activates pancreatic ER kinase (PERK), which coordinates an adaptive program known as the integrated stress response (ISR) by phosphorylating translation initiation factor 2α (eIF2α). There is evidence that the ISR is involved in tumor development. Recent studies also show that the ISR stimulates the expression of vascular endothelial growth factor A (VEGF‐A), a master regulator of angiogenesis. Our previous studies have demonstrated that enforced expression of interferon‐γ (IFNγ) in the central nervous system during development induces sonic hedgehog expression and leads to cerebellar dysplasia or medulloblastoma. Here we report that PERK was activated in cerebellar dysplasia and medulloblastoma in IFNγ‐expressing mice. We found that in... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4944784 Thu, 16 Jun 2011 23:00:00 +0100 4944784 http://www.medworm.com/index.php?rid=4944783&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22694 In this study, we sought to determine whether HLH‐17 functions in dopamine signaling. We found that, unlike wild‐type animals, hlh‐17 animals are resistant to the effects of exogenous dopamine on egg laying and mobility. hlh‐17 animals are also defective in the basal slowing and gustatory plasticity behaviors that require functional dopamine signaling. We also found that the expression of the dopamine receptor genes dop‐1, dop‐2, and dop‐3 and the RGS protein gene egl‐10 is significantly reduced in hlh‐17 animals. Together these results point to a role for HLH‐17 in dopamine signaling in C. elegans. © 2011 Wiley‐Liss, Inc. (Source: Journal of Neuroscience Research) Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4944783 Thu, 16 Jun 2011 23:00:00 +0100 4944783 http://www.medworm.com/index.php?rid=4944782&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22697 AbstractThe antidepressant agomelatine acts as a melatonergic receptor (MT1/MT2) agonist and 5‐HT2C receptor antagonist. Agomelatine has demonstrated efficacy in treating depression, but its neurobiological effects merit further investigation. Preclinical studies reported that agomelatine enhances adult hippocampal neurogenesis and increases expression of several neuroplasticity‐associated molecules. Recently, we showed that agomelatine normalizes hippocampal neuronal activity and promotes neurogenesis in the stress‐compromised brain. To characterize further the effects of this antidepressant in the stressed brain, here we investigated whether it induces changes in the expression of synapsin I (SynI), a regulator of synaptic transmission and plasticity. Adult male rats were subjected... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4944782 Thu, 16 Jun 2011 23:00:00 +0100 4944782 http://www.medworm.com/index.php?rid=4933507&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22692 AbstractThe limited availability and potential to culture primary human brain cells means that there is still a need for cell lines that reliably model human neurons and glial cells. The human‐derived NTera2/D1 (NT2) cell line is a promising tool from which both neuronal (NT2N) and astrocytic (NT2A) cells can be derived in vitro. Here we have investigated the potential to use this cell model to investigate the endocannabinoid system in the CNS. Through immunocytochemical characterization with a range of neuronal and glial markers, we found that these cell lines differentiate into cells with immature neuronal and astrocytic phenotypes, respectively. By real‐time PCR, immunocytochemistry, and functional inhibition of cAMP accumulation, the cannabinoid 1 receptors were identified only on ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4933507 Mon, 13 Jun 2011 23:00:00 +0100 4933507 http://www.medworm.com/index.php?rid=4933506&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22682 In conclusion, this study provides preclinical evidence in support of a beneficial effect of the cannabis‐based medicine Sativex as a neuroprotective agent capable of delaying disease progression in HD, a disorder that is currently poorly managed in the clinic, prompting an urgent need for clinical trials with agents showing positive results in preclinical studies. © 2011 Wiley‐Liss, Inc. (Source: Journal of Neuroscience Research) Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4933506 Mon, 13 Jun 2011 23:00:00 +0100 4933506 http://www.medworm.com/index.php?rid=4933505&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22675 AbstractPituitary adenylyl cyclase‐activating peptide (PACAP; ADCYAP1) is a neuropeptide that regulates a wide array of functions within the brain and periphery. We and others have previously demonstrated that PACAP and its high‐affinity receptor PAC1 are expressed in the embryonic mouse neural tube, suggesting that PACAP plays a role in early brain development. Moreover, we previously showed that PACAP antagonizes the mitotic action of Sonic hedgehog (Shh) in postnatal cerebellar granule precursors. In the present study, we demonstrate that PACAP completely blocked Shh‐dependent motor neuron generation from embryonic stem cell cultures and reduced mRNA levels of the Shh target gene Gli‐1 and several ventral spinal cord patterning genes. In vivo examination of motor neuron and othe... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4933505 Mon, 13 Jun 2011 23:00:00 +0100 4933505 http://www.medworm.com/index.php?rid=4933504&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22654 AbstractNeurofibromatosis 1 (NF1) is an autosomal dominant disease that predisposes individuals to developing benign neurofibromas. Some features and consequences of NF1 appear to result from partial deficiency of neurofibromin (Nfn), the NF1 gene protein product, as a result of haploinsufficiency for the NF1 gene. Other features and consequences of NF1 appear to involve total deficiency of Nfn, which arises as a result of either loss of function of the second NF1 allele or excess degradation of Nfn produced by the second allele in a particular clone of cells. We used immunofluorescence to assess the presence of Nfn in putative Schwann cells (S100B+) and non‐Schwann cells (S100B−) in 36 NF1‐derived benign neurofibromas classified histologically as diffuse or encapsulated. The S100B+/... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4933504 Mon, 13 Jun 2011 23:00:00 +0100 4933504 http://www.medworm.com/index.php?rid=4933503&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22636 AbstractMaternal infection during pregnancy is an environmental risk factor for the offspring to develop severe brain disorders, including schizophrenia. However, little is known about the neurodevelopmental mechanisms underlying the association between prenatal exposure to infection and emergence of cognitive and behavioral dysfunctions later in life. By injecting the viral mimetic polyriboinosinic‐polyribocytidylic acid (Poly I:C) into mice, we investigated the influence of maternal immune challenge during pregnancy on the development of the cerebral cortex, a responsive organ for cognition. Stimulation of the maternal immune system did not influence the cell number or density of the cortical neurons of postnatal 10‐day‐old and 8‐week‐old offspring, whereas gene expressions of ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4933503 Mon, 13 Jun 2011 23:00:00 +0100 4933503 http://www.medworm.com/index.php?rid=4920842&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22689 AbstractEthanol exposure induces neurodegeneration in the developing central nervous system (CNS). Fetal alcohol spectrum disorders (FASD) are caused by ethanol exposure during pregnancy and are the most common nonhereditary cause of mental retardation. It is important to identify agents that provide neuroprotection against ethanol neurotoxicity. Multiple mechanisms have been proposed for ethanol‐induced neurodegeneration, and oxidative stress is one of the most important mechanisms. Recent evidence indicates that glycogen synthase kinase 3β (GSK3β) is a potential mediator of ethanol‐mediated neuronal death. Cyanidin‐3‐glucoside (C3G), a member of the anthocyanin family, is a potent natural antioxidant. Our previous study suggested that C3G inhibited GSK3β activity in neurons. U... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4920842 Sat, 11 Jun 2011 04:53:00 +0100 4920842 http://www.medworm.com/index.php?rid=4920845&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22688 AbstractPurkinje cell protein 4 (PCP4), also called brain‐specific polypeptide 19 (PEP19), is a neurospecific, small calmodulin‐binding protein that binds both calcium‐free and calcium‐binding calmodulin to regulate the calmodulin‐mediated signal. The expression level of this molecule is decreased in the brain in Alzheimer's disease, Huntington's disease, and alcoholism. However, little is known of the function of PCP4 regarding neuronal or neuroendocrine cell differentiation and neurotransmitter release. To address this, we established a PCP4 tetracycline‐inducible rat chromaffin cell line, PC12. When PCP4 expression was induced with doxcycline, neurite outgrowth was significantly advanced in the presence of nerve growth factor (NGF) and dibutyryl cAMP, which was inhibited by ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4920845 Thu, 09 Jun 2011 23:00:00 +0100 4920845 http://www.medworm.com/index.php?rid=4920844&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22678 AbstractHuman T‐cell leukemia virus type I (HTLV‐I)‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease characterized by selective loss of axons and myelin in the corticospinal tracts. This central axonopathy may originate from the impairment of anterograde axoplasmic transport. Previous work showed tau hyperphosphorylation at T181 in cerebrospinal fluid of HAM/TSP patients. Similar hyperphosphorylation occurs in SH‐SY5Y cells incubated with supernatant from MT‐2 cells (HTLV‐I‐infected lymphocytes secreting viral proteins, including Tax) that produce neurite shortening. Tau phosphorylation at T181 is attributable to glycogen synthase kinase 3‐β (GSK3‐β) and cyclin‐dependent kinase 5 (CDK5) activation. Here we investigate whether... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4920844 Thu, 09 Jun 2011 23:00:00 +0100 4920844 http://www.medworm.com/index.php?rid=4920843&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22681 In this study, we have evaluated the neuroprotective effect of guanosine against glutamate‐induced toxicity in hippocampal slices and the mechanism involved in such an effect. We have found that guanosine (100 μM) was neuroprotective against 1 mM glutamate‐induced cell death through the inhibition of glutamate release induced by glutamate. Guanosine also induced the phosphorylation and, thus, activation of protein kinase B (PKB/Akt), a downstream target of phosphatidylinositol‐3 kinase (PI3K), as well as phosphorylation of glycogen synthase kinase 3β, which has been reported to be inactivated by Akt after phosphorylation at Ser9. Glutamate treated hippocampal slices showed increased inducible nitric oxide synthase (iNOS) expression that was prevented by guanosine. Slices preincubat... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4920843 Thu, 09 Jun 2011 23:00:00 +0100 4920843 http://www.medworm.com/index.php?rid=4911145&cid=s_33652_168_f&fid=33652&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fjnr.22687 AbstractMitochondria are central integrators and transducers of proapoptotic signals for neuronal apoptosis. The tumor suppressor protein p53 can trigger apoptosis independently of its transcriptional activity, through subcellular translocation of cytochrome c and caspase activation. To define better the proapoptotic role of p53 under various stress conditions, we investigated the protein levels of p53 and cytochrome c in mitochondrial and cytosolic fractions, as well as caspase‐3 activation and apoptosis, in the prefrontal cortex and hippocampus of male Wistar rats subjected to acute, chronic, or combined stressors. Mitochondrial p53 can suppress the antioxidant enzyme MnSOD, so its activity was also determined. In the prefrontal cortex, but not in hippocampus, increased protein levels ... Journal of Neuroscience Research journals http://www.medworm.com/rss/comments.php?id=4911145 Thu, 09 Jun 2011 01:32:43 +0100 4911145