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 Neurochemistry' source. Wed, 08 Feb 2012 20:43:14 +0100 http://www.medworm.com/index.php?rid=5668647&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07685.x AbstractThe nicotinic acetylcholine receptor (nAChR) β3 subunit is thought to serve an accessory role in nAChR subtypes expressed in dopaminergic regions implicated in drug dependence and reward. When β3 subunits are expressed in excess, they have a dominant‐negative effect on function of selected nAChR subtypes. Here, we show, in Xenopus oocytes expressing α2, α3 or α4 plus either β2 or β4 subunits, that in the presumed presence of similar amounts of each nAChR subunit, co‐expression with wild‐type β3 subunits generally (except for α3*‐nAChR) lowers amplitudes of agonist‐evoked, inward peak currents by 20‐50% without having dramatic effects (<2‐fold) on agonist potencies. By contrast, co‐expression with mutant β3V9’S subunits generally (except for α4β2*‐... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5668647 Mon, 06 Feb 2012 05:00:00 +0100 5668647 http://www.medworm.com/index.php?rid=5668646&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07684.x In this study, we provide evidence that synaptic vesicles are also capable of synthesizing the vesicular glutamate transporter substrate glutamate, from α‐ketoglutarate and L‐aspartate (as the amino group donor); glutamate thus produced is taken up into vesicles. We also report a finding that α‐ketoglutarate‐derived glutamate uptake into synaptic vesicles and aspartate aminotransferase are inhibited by 2,3‐pyrazinedicarboxylate. Evidence is given that this is a selective inhibitor for aspartate aminotransferase. These observations provide insight into understanding the nerve endings’ mechanism for high efficiency in glutamate transmission. Finding this inhibitor may have implications for further experimentation on the role of α‐ketoglutarate‐derived glutamate in glutamat... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5668646 Mon, 06 Feb 2012 05:00:00 +0100 5668646 http://www.medworm.com/index.php?rid=5660862&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07679.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5660862 Fri, 03 Feb 2012 05:00:00 +0100 5660862 http://www.medworm.com/index.php?rid=5660861&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07680.x Abstractβ‐site APP cleaving enzyme 1 (BACE1) is the transmembrane aspartyl protease that catalyzes the first cleavage step in the proteolysis of the amyloid β‐protein precursor (APP) to the amyloid β‐protein (Aβ), a process involved in the pathogenesis of Alzheimer disease. BACE1 pre‐mRNA undergoes complex alternative splicing, the regulation of which is not well understood. We identified a G‐rich sequence within exon 3 of BACE1 involved in controlling splice site selection. Mutation of the G‐rich sequence decreased use of the normal 5’ splice site of exon 3, which leads to full‐length and proteolytically active BACE1, and increased use of an alternative splice site, which leads to a shorter, essentially inactive isoform. Nuclease protection assays, nuclear magnetic res... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5660861 Fri, 03 Feb 2012 05:00:00 +0100 5660861 http://www.medworm.com/index.php?rid=5660860&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07681.x AbstractInsulin offers trophic support through receptors expressed widely on peripheral neurons. In this work, we studied whether peripheral sensory neurons demonstrate resistance to its trophic properties, a property relevant during type 2 diabetes mellitus or following supraphysiological therapy. Insulin receptors (IRs) were not only localized to neuronal membranes and cytoplasm but also had a unique, previously unrecognized localization to neuronal nuclei. We confirmed that nanomolar doses increased neurite outgrowth of adult sensory neurons, but in response to micromolar doses of insulin, even following a brief two hour exposure, survival and outgrowth of neurites were blunted. Neurons exposed to picomolar insulin concentrations in their media for 5d had resistance to the impact of lat... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5660860 Fri, 03 Feb 2012 05:00:00 +0100 5660860 http://www.medworm.com/index.php?rid=5668645&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07682.x AbstractCynandione A, an acetophenone from the roots of Cynanchum auriculatum and other species in the genus attenuates neurotoxicity of a variety of neurotoxic agents such as L‐glutamate in vitro. Here, we sought to further characterize the neuroprotective effects of cynandione A and other acetophenones from the roots of C. auriculatum in pheochromocytoma tumor cell line PC12 and investigate whether cynandione A protected against ischemic injuries in rats with experimentally induced cerebral ischemia. Viability assays using the WST‐8 method and LDH release assays showed that cynandione A dose‐dependently attenuated glutamate‐induced cytotoxicity. Comparative proteomic analysis by two‐dimensional gel electrophoresis and MALDI‐TOF MS/MS of PC12 cells treated with cynandione A sh... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5668645 Wed, 01 Feb 2012 05:00:00 +0100 5668645 http://www.medworm.com/index.php?rid=5660859&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07683.x Conclusions:  Increased desmoplakin I levels, determined within 1 to 3 months of the first ischemic stroke, could be a biomarker for statin responsiveness against a new vascular event in post‐ischemic stroke patients taking statins early (1 to 3 months) after the ischemic stroke.© 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5660859 Wed, 01 Feb 2012 05:00:00 +0100 5660859 http://www.medworm.com/index.php?rid=5649980&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07677.x In this study we used in vivo fast scan cyclic voltammetry (FSCV) in the NAc of awake, freely moving rats. The experiments were primarily designed to capture changes in dopamine due to phasic firing – that is, the measurement of dopamine ‘transients’. These FSCV measurements revealed for the first time that spontaneous dopamine transients constitute a major component of extracellular dopamine levels in the NAc. A series of experiments were designed to probe regulation of extracellular dopamine. Lidocaine was infused into the ventral tegmental area, the site of dopamine cell bodies, to arrest neuronal firing. While there was virtually no instantaneous change in dopamine concentration, longer sampling revealed a decrease in dopamine transients and a time‐averaged decrease in the extr... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5649980 Wed, 01 Feb 2012 05:00:00 +0100 5649980 http://www.medworm.com/index.php?rid=5649979&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07678.x In this study, the effects of chronic cocaine abuse on Ng expression in euthyroid and hypothyroid mice were assessed. In cocaine‐treated mice, decreased Ng expression was observed in the absence of changes in levels of thyroid hormones or other HPT signaling factors. Therefore, we hypothesized that cocaine decreases Ng expression via alterations in 9‐cis‐RA availability and TR/RXR signaling. In support of this hypothesis, RXR‐γ was significantly decreased in brains of cocaine‐treated mice while CYP26A1, the main enzyme responsible for neuronal RA degradation, was significantly increased. Results from this study provide the first evidence for a direct effect of cocaine abuse on TR/RXR signaling, RA metabolism, and transcriptional regulation of Ng, a gene essential for adult neuro... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5649979 Wed, 01 Feb 2012 05:00:00 +0100 5649979 http://www.medworm.com/index.php?rid=5649981&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07676.x In this report we cloned and functionally characterized the human ATP13A2 gene promoter. We showed that the promoter region of the human ATP13A2 gene contains hypoxia response elements (HREs) which can bind to transcription factor hypoxia‐inducible factor 1α (HIF‐1α). Hypoxia upregulated ATP13A2 transcription via HIF‐1α in HEK293 and dopaminergic MN9D cells. Our study indicates that hypoxia signaling plays a very important role in the regulation of human ATP13A2 gene expression. Further study is needed to determine the role of hypoxia in the pathogenesis of PD and its interaction with other PD causative genes, which will provide insights to the role of hypoxia and dysregulation of gene expression in Parkinson’s disease.© 2012 The Authors Journal of Neurochemistry © 2012 Intern... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5649981 Tue, 31 Jan 2012 05:00:00 +0100 5649981 http://www.medworm.com/index.php?rid=5649984&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07674.x AbstractIn the present study a possible sertraline action on cerebral presynaptic Na+ channels was investigated. For this purpose, the effect of sertraline on responses induced by the Na+ channel opener, veratridine, namely the increase in Na+ and in neurotransmitter release in hippocampus isolated nerve endings was investigated. Results show that sertraline in the low μM range (1.5 to 25 μM) progressively inhibits the rise in Na+ and the release of preloaded [3H]Glu as well as the release of endogenous 5‐HT, Glu and GABA (detected by HPLC) induced by veratridine depolarization either under external Ca2+‐free conditions or in the presence of external Ca2+. In addition, under non depolarized conditions, sertraline (25 μM) increased the external concentration of 5‐HT at expense of i... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5649984 Mon, 30 Jan 2012 05:00:00 +0100 5649984 http://www.medworm.com/index.php?rid=5649983&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07673.x AbstractThe endogenous neurotransmitter noradrenaline (NA) plays several roles in maintaining brain homeostasis, including exerting anti‐inflammatory and neuroprotective effects. The primary source of NA in the CNS are tyrosine hydroxylase (TH) positive neurons located in the Locus coeruleus (LC) which send projections throughout the brain and spinal cord. We recently demonstrated that dysregulation of the LC:Noradrenergic system occurs in experimental autoimmune encephalomyelitis (EAE) as well as in MS patients, associated with damage occurring to LC neurons. Vindeburnol, a structural analog of the cerebral vasodilator vincamine, was previously reported to increase TH expression and activity in LC neurons. Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein (MOG)... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5649983 Mon, 30 Jan 2012 05:00:00 +0100 5649983 http://www.medworm.com/index.php?rid=5649982&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07675.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5649982 Mon, 30 Jan 2012 05:00:00 +0100 5649982 http://www.medworm.com/index.php?rid=5621217&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07671.x AbstractImpairment of cognitive functions including hippocampus‐dependent spatial learning and memory affects nearly half of the aged population. Age‐related cognitive decline is associated with synaptic dysfunction that occurs in the absence of neuronal cell loss, suggesting that impaired neuronal signaling and plasticity may underlie age‐related deficits of cognitive function. Expression of myelin‐associated inhibitors (MAIs) of synaptic plasticity, including the ligands MAG, Nogo‐A, and OMgp, and their common receptor, NgR1, was examined in hippocampal synaptosomes and CA1, CA3 and DG subregions derived from adult (12‐13 months) and aged (26‐28 months) Fischer 344 x Brown Norway rats. Rats were behaviorally phenotyped by Morris water maze testing and classified as aged cog... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5621217 Tue, 24 Jan 2012 01:01:24 +0100 5621217 http://www.medworm.com/index.php?rid=5621226&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07663.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5621226 Mon, 23 Jan 2012 05:00:00 +0100 5621226 http://www.medworm.com/index.php?rid=5621225&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07662.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5621225 Mon, 23 Jan 2012 05:00:00 +0100 5621225 http://www.medworm.com/index.php?rid=5621224&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07656.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5621224 Mon, 23 Jan 2012 05:00:00 +0100 5621224 http://www.medworm.com/index.php?rid=5621218&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07670.x AbstractSeizures that are resistant to standard medications remain a major clinical problem. One underutilized option for patients with medication‐resistant seizures is the high‐fat, low‐carbohydrate ketogenic diet. The diet received its name based on the observation that patients consuming this diet produce ketone bodies (e.g., acetoacetate, β‐hydroxybutyrate, and acetone). Although the exact mechanisms of the diet are unknown, ketone bodies have been hypothesized to contribute to the anticonvulsant and antiepileptic effects. In this review, anticonvulsant properties of ketone bodies and the ketogenic diet are discussed (including GABAergic and glutamatergic effects). Because of the importance of ketone body metabolism in the early stages of life, the effects of ketone bodies on ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5621218 Mon, 23 Jan 2012 05:00:00 +0100 5621218 http://www.medworm.com/index.php?rid=5610976&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07669.x AbstractAmmonia is responsible for cerebral edema (CE) associated with acute liver failure (ALF), but the role of the vasogenic mechanism has been a matter of dispute. Here, we tested the hypothesis that ammonia induces changes in blood‐brain barrier (BBB) permeability by a mechanism coupled to oxidative/ nitrosative stress (ONS) evoked in the BBB‐forming cerebral capillary endothelial cells. Treatment of a rat brain endothelial cell line (RBE‐4) with ammonia (5 mmol/L, 24h) caused accumulation of ONS markers: reactive oxygen species (ROS), nitric oxide (NO) and peroxidation products of phospholipid‐bound arachidonic acid, F2‐isoprostanes (F2‐IsoPs). Concurrently, ammonia increased the activity of extracellular matrix metalloproteinases (MMP‐2/ MMP‐9), increased cell permea... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5610976 Sat, 21 Jan 2012 00:51:57 +0100 5610976 http://www.medworm.com/index.php?rid=5610977&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07668.x AbstractType 2 diabetes mellitus is thought to be a significant risk factor for Alzheimer’s disease. Insulin resistance also affects the CNS by regulating key processes, such as neuronal survival and longevity, learning and memory. However, the mechanisms underlying these effects remain uncertain. To investigate whether insulin resistance is associated with the assembly of amyloid ß‐protein at the cell surface of neurons, we inhibited insulin‐signalling pathways of primary neurons. The treatments of insulin receptor (IR)‐knockdown and a phosphatidylinositol 3‐kinase inhibitor (LY294002), but not an extracellular signal‐regulated kinase inhibitor, induced an increase in GM1 ganglioside levels in detergent‐resistant membrane microdomains of the neurons. The aged db/db mouse br... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5610977 Thu, 19 Jan 2012 05:00:00 +0100 5610977 http://www.medworm.com/index.php?rid=5599314&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07611.x In this study, we report a novel interaction between a ligand‐gated ion channel and a G‐protein coupled receptor which regulates glutamate release from parallel fiber axon terminals. Immunocytochemical analysis revealed that GABAA receptors and the high affinity group III metabotropic glutamate receptor subtype 4 (mGlu4) are co‐localized on glutamatergic parallel fiber axon terminals in the cerebellum. GABAA and mGlu4 receptors were also found to co‐immunoprecipitate from cerebellar membranes. Independently, these two receptors have opposing roles on glutamate release: pre‐synaptic GABAA receptors promote, while mGlu4 receptors inhibit, glutamate release. However, coincident activation of GABAA receptors with muscimol and mGlu4 with the agonist (2S)‐S‐2‐amino‐4‐phosphon... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5599314 Wed, 18 Jan 2012 01:52:05 +0100 5599314 http://www.medworm.com/index.php?rid=5599313&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07593.x We report here that a significant enhancement in apoptosis in rat cerebellar granule neurons (CGNs) was observed upon incubation with 5 mM K+/serum free (LK‐S) medium. Cholesterol enrichment further potentiated CGN apoptosis incubated under LK‐S medium. On the contrary, cholesterol depletion using methyl‐beta‐cyclodextrin protected the CGNs from apoptosis induced by LK‐S treatment. Cholesterol enrichment, however, did not induce apoptosis in CGNs that have been incubated with 25 mM K+/serum medium. Mechanistically, increased IK currents and DNA fragmentation were found in CGNs incubated in LK‐S, which was further potentiated in the presence of cholesterol. Cholesterol‐treated CGNs also exhibited increased cAMP levels and up‐regulation of Kv2.1 expression. Increased leve... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5599313 Wed, 18 Jan 2012 01:51:59 +0100 5599313 http://www.medworm.com/index.php?rid=5599278&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07667.x AbstractHere we report that ST101 (spiro[imidazo[1,2‐a]pyridine‐3,2‐indan]‐2(3H)‐one; previously coded as ZSET1446) targets T‐type voltage‐gated calcium channels in mediating improved cognition in the central nervous system. We prepared rat somatosensory cortical and hippocampal slices, treated them with 0.01 to 100 nM ST101, and performed immunoblotting and electrophysiological analyses using various voltage‐gated calcium channel (VGCC) inhibitors. Treatment of rat cortical slices with a range of ST101 concentrations significantly increased CaMKII autophosphorylation following a bell‐shaped dose‐response curve, with 0.1 nM ST101 representing the maximally effective concentration. PKCα autophosphorylation was also significantly increased by 0.1 nM ST101 treatment. ST10... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5599278 Wed, 18 Jan 2012 01:49:43 +0100 5599278 http://www.medworm.com/index.php?rid=5660863&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07667.x In this study, we report that spiro[imidazo[1,2‐a]pyridine‐3,2‐indan]‐2(3H)‐one (ST101; previously coded as ZSET1446) targets T‐type voltage‐gated calcium channels in mediating improved cognition in the CNS. We prepared rat somatosensory cortical and hippocampal slices, treated them with 0.01 to 100 nM ST101, and performed immunoblotting and electrophysiological analyses using various voltage‐gated calcium channel (VGCC) inhibitors. Treatment of rat cortical slices with a range of ST101 concentrations significantly increased calcium/calmodulin‐dependent protein kinase II (CaMKII) autophosphorylation following a bell‐shaped dose–response curve, with 0.1 nM ST101 representing the maximally effective concentration. protein kinase Cα autophosphorylation was also signif... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5660863 Tue, 17 Jan 2012 05:00:00 +0100 5660863 http://www.medworm.com/index.php?rid=5599281&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07665.x AbstractKainate receptors (KARs) have been described as modulators of synaptic transmission at different synapses. However, this role of KARs has not been well characterized in the amygdala. We have explored the effect of kainate receptor activation at the synapse established between fibers originating at medial geniculate nucleus and the principal cells in the lateral amygdala. We have observed an inhibition of evoked excitatory synaptic currents (eEPSCs) amplitude after a brief application of KARs agonists KA and ATPA. Paired‐pulse recordings showed a clear pair pulse facilitation that was enhanced after KA or ATPA application. When postsynaptic cells were loaded with BAPTA, the depression of eEPSC amplitude observed after the perfusion of KAR agonists was not prevented. We have also o... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5599281 Tue, 17 Jan 2012 05:00:00 +0100 5599281 http://www.medworm.com/index.php?rid=5599280&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07664.x AbstractNeuroglial cells define brain homeostasis and mount defense against pathological insults. Astroglia regulate neurogenesis and development of brain circuits. In the adult brain, astrocytes enter into intimate dynamic relationship with neurons, especially at synaptic sites where they functionally form the tripartite synapse. At these sites astrocytes regulate ion and neurotransmitter homeostasis, metabolically support neurons and monitor synaptic activity; one of the readouts of the latter manifests in astrocytic intracellular Ca2+ signals. This form of astrocytic excitability can lead to release of chemical transmitters via Ca2+‐dependent exocytosis. Once in the extracellular space, gliotransmitters can modulate synaptic plasticity and cause changes in behavior. Besides these phys... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5599280 Tue, 17 Jan 2012 05:00:00 +0100 5599280 http://www.medworm.com/index.php?rid=5599279&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07666.x Abstract20‐hydroxyeicosatetraenoic acid (20‐HETE) is a cytochrome P450 (CYP) metabolite of arachidonic acid that that contributes to infarct size following focal cerebral ischemia. However, little is known about the role of 20‐HETE in global cerebral ischemia or neonatal hypoxia‐ischemia (H‐I). The present study examined the effects of blockade of the synthesis of 20‐HETE with HET0016 in neonatal piglets after H‐I to determine if it protects highly vulnerable striatal neurons. Administration of HET0016 after H‐I improved early neurological recovery and protected neurons in putamen after 4 days of recovery. HET0016 had no significant effect on cerebral blood flow. CYP 4A immunoreactivity was detected in putamen neurons, and direct infusion of 20‐HETE in the putamen increas... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5599279 Tue, 17 Jan 2012 05:00:00 +0100 5599279 http://www.medworm.com/index.php?rid=5668648&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07660.x This study describes the effects of long‐chain fatty acids on inflammatory signaling in cultured astrocytes. Data show that the saturated fatty acid palmitic acid, as well as lauric acid and stearic acid, trigger the release of TNFα and IL‐6 from astrocytes. Unsaturated fatty acids were unable to induce cytokine release from cultured astrocytes. Furthermore, the effects of palmitic acid on cytokine release require Toll‐like receptor 4 rather than CD36 or Toll‐like receptor 2, and do not depend on palmitic acid metabolism to palmitoyl‐CoA. Inhibitor studies revealed that pharmacologic inhibition of p38 or p42/44 MAPK pathways prevents the pro‐inflammatory effects of palmitic acid, whereas JNK and PI3K inhibition does not affect cytokine release. Depletion of microglia from prim... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5668648 Mon, 16 Jan 2012 05:00:00 +0100 5668648 http://www.medworm.com/index.php?rid=5599283&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07660.x This study describes the effects of long‐chain fatty acids on inflammatory signaling in cultured astrocytes. Data show that the saturated fatty acid palmitic acid, as well as lauric acid and stearic acid, trigger the release of TNFα and IL‐6 from astrocytes. Unsaturated fatty acids were unable to induce cytokine release from cultured astrocytes. Furthermore, the effects of palmitic acid on cytokine release require TLR4 rather than CD36 or TLR2, and do not depend on palmitic acid metabolism to palmitoyl‐CoA. Inhibitor studies revealed that pharmacologic inhibition of p38 or p42/44 MAPK pathways prevents the pro‐inflammatory effects of palmitic acid, while JNK and PI3K inhibition does not affect cytokine release. Depletion of microglia from primary astrocyte cultures using the lysos... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5599283 Mon, 16 Jan 2012 05:00:00 +0100 5599283 http://www.medworm.com/index.php?rid=5599282&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07661.x AbstractChronic nicotine and oral contraceptive (NOC) exposure caused significant loss of hippocampal membrane‐bound estrogen receptor‐beta (ER‐β) in female rats compared with exposure to nicotine alone. Mitochondrial ER‐β regulates estrogen‐mediated mitochondrial structure and function; therefore, investigating the impact of NOC on mitochondrial ER‐β and its function could help delineate the harmful synergism between nicotine and OC. In the current study, we tested the hypothesis that NOC‐induced loss of mitochondrial ER‐β alters the oxidative phosphorylation system protein levels and mitochondrial respiratory function. This hypothesis was tested in hippocampal mitochondria isolated from female rats exposed to saline, nicotine, OC or NOC for 16 days. NOC decreased the ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5599282 Mon, 16 Jan 2012 05:00:00 +0100 5599282 http://www.medworm.com/index.php?rid=5599285&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07658.x AbstractCell adhesion molecules of the immunoglobulin superfamily (IgCAMs) have been shown to modulate growth factor signaling and follow complex trafficking pathways in neurons. Similarly, several growth factors, including members of the neurotrophin family, undergo axonal retrograde transport that is required to elicit their full signaling potential in neurons. We sought to determine whether IgCAMs that enter the axonal retrograde transport route co‐operate with neurotrophin signaling. We identified Activated Leukocyte Cell Adhesion Molecule (ALCAM), a protein involved in axon pathfinding and development of the neuromuscular junction, to be associated with an axonal endocytic compartment that contains neurotrophins and their receptors. Although ALCAM enters carriers that are transporte... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5599285 Fri, 13 Jan 2012 05:00:00 +0100 5599285 http://www.medworm.com/index.php?rid=5599284&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07659.x AbstractMicroglia express three isoforms of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, Nox1, Nox2 and Nox4, with the potential to produce superoxide (O2.‐). Microglia also express neurotransmitter receptors, which can modulate microglial responses. Here microglial activity of Nox1, Nox2 and Nox4 in primary rat cultured microglia or the rodent BV2 cell line were altered by microglial neurotransmitter receptor modulation. Glutamate, GABA or ATP triggered microglial O2.‐ production via Nox activation. Nox activation was elicited by agonists of metabotropic mGlu3 receptors and by group III receptors, by GABAA but not GABAB receptors, and by purinergic P2X7 or P2Y2/4 receptors but not P2Y1 receptors, and inhibited by mGluR5 antagonists. The neurotransmitters also modul... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5599284 Fri, 13 Jan 2012 05:00:00 +0100 5599284 http://www.medworm.com/index.php?rid=5599286&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07657.x AbstractC3 ADP‐ribosyltransferase is a valuable tool to study Rho‐dependent cellular processes. In the current study we investigated the impact of enzyme‐deficient peptides derived from Clostridium botulinum C3 transferase in the context of neuronal process elongation and branching, synaptic connectivity, and putative beneficial effects on functional outcome following traumatic injury to the CNS. By screening a range of peptidic fragments we identified three short peptides from C3bot that promoted axon and dendrite outgrowth in cultivated hippocampal neurons. Furthermore, one of these fragments, a 26‐amino acid peptide covering the residues 156‐181 enhanced synaptic connectivity in primary hippocampal culture. This peptide was also effective to foster axon outgrowth and re‐inne... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5599286 Thu, 12 Jan 2012 05:00:00 +0100 5599286 http://www.medworm.com/index.php?rid=5599287&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07655.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5599287 Tue, 10 Jan 2012 05:00:00 +0100 5599287 http://www.medworm.com/index.php?rid=5573021&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07561.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5573021 Mon, 09 Jan 2012 00:41:27 +0100 5573021 http://www.medworm.com/index.php?rid=5573017&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07654.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5573017 Mon, 09 Jan 2012 00:39:04 +0100 5573017 http://www.medworm.com/index.php?rid=5573019&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07652.x AbstractAquaporin‐4, a predominant water channel in the brain, is specifically expressed in astrocyte endfeet and plays a central role in water homeostasis, neuronal activity, and cell migration in the brain. It has two dominant isoforms called M1 and M23, whose mRNA is driven by distinct promoters located upstream of exons 0 and 1 of the aquaporin‐4 gene, respectively. To identify cis‐acting elements responsible for the astrocyte‐specific transcription of M1 mRNA, the promoter activity of the 5′‐flanking region upstream of exon 0 in primary cultured mouse astrocytes was examined by luciferase assay, and sequences, where nuclear factors bind, were identified by electrophoretic mobility shift assay. An astrocyte‐specific activity enhancing transcription from the M1 promoter wa... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5573019 Sat, 07 Jan 2012 05:00:00 +0100 5573019 http://www.medworm.com/index.php?rid=5573018&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07653.x AbstractIn the mammalian brain, the α7 nicotinic and NMDA receptor antagonist kynurenic acid is synthesized by irreversible enzymatic transamination of the tryptophan metabolite L‐kynurenine. D‐kynurenine, too, serves as a bioprecursor of kynurenic acid in several organs including the brain, but the conversion is reportedly catalyzed through oxidative deamination by D‐aminoacid oxidase. Using brain and liver tissue homogenates from rats and humans, and conventional incubation conditions for kynurenine aminotransferases, we show here that KYNA production from D‐kynurenine, like the more efficient kynurenic acid synthesis from L‐kynurenine, is blocked by the aminotransferase inhibitor aminooxyacetic acid. In vivo, focal application of 100 μM D‐kynurenine by reverse microdialysi... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5573018 Sat, 07 Jan 2012 05:00:00 +0100 5573018 http://www.medworm.com/index.php?rid=5561944&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07646.x AbstractSerine hydroxymethyltransferase (SHMT) catalyzes the transfer of a beta carbon from serine to tetrahydrofolate (THF) to form glycine and 5,10‐methylene‐THF. This reaction plays an important role in neurotransmitter synthesis and metabolism. We set out to resequence SHMT1 and SHMT2, followed by functional genomic studies. We identified 87 and 60 polymorphisms in SHMT1 and SHMT2, respectively. We observed no significant functional effect of the 13 nonsynonymous SNPs in these genes, either on catalytic activity or protein quantity. We imputed additional variants across the two genes using “1000 Genomes” data, and identified 14 variants that were significantly associated (p‐value < 1.0E‐10) with SHMT1 mRNA expression in lymphoblastoid cell lines. Many of these SNPs were ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5561944 Thu, 05 Jan 2012 05:00:00 +0100 5561944 http://www.medworm.com/index.php?rid=5561943&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07647.x AbstractAll‐trans‐retinal and its condensation‐products can cause retinal degeneration in a light−dependent manner and contribute to the pathogenesis of human macular diseases such as Stargardt’s disease and age−related macular degeneration (AMD). Although these toxic retinoid by−products originate from rod and cone photoreceptor cells, the contribution of each cell type to light−induced retinal degeneration is unknown. Here the primary objective was to learn whether rods or cones are more susceptible to light−induced, all−trans−retinal−mediated damage. Previously, we reported that mice lacking enzymes that clear all−trans−retinal from the retina, ATP−binding cassette transporter 4 (ABCA4) and retinol dehydrogenase 8 (RDH8), manifested light‐induced retinal ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5561943 Thu, 05 Jan 2012 05:00:00 +0100 5561943 http://www.medworm.com/index.php?rid=5561942&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07648.x AbstractCbln1 is essential for synapse integrity in cerebellum through assembly into complexes that bridge presynaptic β‐neurexins (Nrxn) to postsynaptic GluRδ2. However, GluRδ2 is largely cerebellum‐specific, yet Cbln1 and its little studied family members, Cbln2 and Cbln4, are expressed throughout brain. Therefore, we investigated whether additional proteins mediate Cbln family actions. Whereas Cbln1 and Cbln2 bound to GluRδ2 and Nrxns1‐3, Cbln4 bound weakly or not at all, suggesting it has distinct binding partners. In a candidate receptor‐screening assay, Cbln4 (but not Cbln1 or Cbln2) bound selectively to the netrin receptor, DCC (deleted in colorectal cancer) in a netrin‐displaceable fashion. To determine whether Cbln4 had a netrin‐like function, Cbln4‐null mice wer... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5561942 Thu, 05 Jan 2012 05:00:00 +0100 5561942 http://www.medworm.com/index.php?rid=5561941&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07649.x AbstractChronic intake of high fat diet is known to alter brain neurotransmitter systems that participate in the central regulation of food intake. Dopamine (DA) system changes in response to high fat diet have been observed in the hypothalamus, important in the homeostatic control of food intake, as well as within the central reward circuitry (ventral tegmental area (VTA), nucleus accumbens (NAc) and prefrontal cortex (PFC)), critical for coding the rewarding properties of palatable food and important in hedonically‐driven feeding behavior. Using a mouse model of diet‐induced obesity (DIO), significant alterations in expression in dopamine‐related genes were documented in adult animals, and the general pattern of gene expression changes was opposite within the hypothalamus versus th... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5561941 Thu, 05 Jan 2012 05:00:00 +0100 5561941 http://www.medworm.com/index.php?rid=5561940&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07650.x AbstractCyclin dependent kinase‐5 (cdk5)/p35 and protein phosphatase‐1 (PP1) are two major enzymes that control a variety of physiological processes within the nervous system including neuronal differentiation, synaptic plasticity and axonal transport. Defective cdk5/p35 and PP1 function are also implicated in several major human neurodegenerative diseases. Cdk5/p35 and the catalytic subunit of PP1 (PP1C) both bind to the brain enriched, serine‐threonine kinase lemur tyrosine kinase‐2 (LMTK2). Moreover, LMTK2 phosphorylates PP1C on threonine‐320 (PP1Cthr320) to inhibit its activity. Here we demonstrate that LMTK2 is phosphorylated on serine‐1418 (LMTK2ser1418) by cdk5/p35 and present evidence that this regulates its ability to phosphorylate PP1Cthr320. We thus describe a new si... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5561940 Thu, 05 Jan 2012 05:00:00 +0100 5561940 http://www.medworm.com/index.php?rid=5561947&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07627.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5561947 Wed, 04 Jan 2012 05:00:00 +0100 5561947 http://www.medworm.com/index.php?rid=5649985&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07645.x In this study, we show that in astrocytes the NAD+/NADH redox state modulates dopamine‐induced Ca2+ signals thereby connecting metabolism and Ca2+ signaling. Application of dopamine induced a dose‐dependent increase in Ca2+ signal frequency in these cells, which was dependent on D1‐receptor signaling, glycolytic activity, an increase in cytosolic NADH and inositol 1,4,5‐triphosphate receptor operated intracellular Ca2+ stores. Application of dopamine at a low concentration (1 μM) did not induce an increase in Ca2+ signal frequency by itself. However, simultaneously increasing cytosolic NADH content either by direct application of NADH or by application of lactate resulted in a pronounced increase in Ca2+ signal frequency. This increase could be blocked by co‐application of pyr... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5649985 Mon, 02 Jan 2012 05:00:00 +0100 5649985 http://www.medworm.com/index.php?rid=5561945&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07645.x AbstractAstrocytes are important glial cells in the brain providing metabolic support to neurons as well as contributing to brain signaling. These different functional levels have to be highly coordinated to allow for proper cell and brain function. Here we show that in astrocytes the NAD+/NADH redox state modulates dopamine induced Ca2+‐signals thereby connecting metabolism and Ca2+‐signaling. Application of dopamine induced a dose dependent increase in Ca2+‐signal frequency in these cells, which was dependent on D1‐receptor signaling, glycolytic activity, an increase in cytosolic NADH and inositol 1,4,5‐triphosphate receptor operated intracellular Ca2+‐stores. Application of dopamine at a low concentration (1 μM) did not induce an increase in Ca2+‐signal frequency by itsel... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5561945 Mon, 02 Jan 2012 05:00:00 +0100 5561945 http://www.medworm.com/index.php?rid=5561939&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2012.07651.x AbstractThe repellent semaphorin 3A (Sema3A) causes growth cone turning or collapse by triggering cytoskeletal rearrangements and detachment of adhesion sites. Growth cone detachment is dependent on eicosanoid activation of protein kinase C epsilon (PKCε), but the characterization of the phospholipase A2 (PLA2) that releases arachidonic acid (AA) for eicosanoid synthesis has remained elusive. Here we show in rat dorsal root ganglion neurons that Sema3A stimulates PLA2 activity, that Sema3A‐induced growth cone turning and collapse are dependent on the release of AA, and that the primary PLA2 involved is the Group IV α isoform (GIVA). Silencing GIVA expression renders growth cones resistant to Sema3A‐induced collapse, and GIVA inhibition reverses Sema3A‐induced repulsion into attract... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5561939 Sun, 01 Jan 2012 05:00:00 +0100 5561939 http://www.medworm.com/index.php?rid=5553265&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07644.x AbstractDeposition of amyloid β protein (Aβ) in the brain is the hallmark of Alzheimer’s Disease (AD) pathogenesis. Beta‐site APP cleaving enzyme 1 (BACE1) is the β‐secretase in vivo essential for generation of Aβ. Previously we demonstrated that BACE1 is ubiquitinated and the degradation of BACE1 is mediated by the ubiquitin‐proteasome pathway (UPP). However the mechanism underlying regulation of BACE1 degradation by UPP remains elusive. Ubiquitin carboxyl‐terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme highly specific to neuron, catalyzing the hydrolysis of ubiquitin conjugates from ubiquitinated substrates. UCHL1 regulates ubiquitin‐dependent protein degradation. However, whether UCHL1 is particularly involved in the proteasomal degradation of BACE1 and what i... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5553265 Sat, 31 Dec 2011 23:33:05 +0100 5553265 http://www.medworm.com/index.php?rid=5553267&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07642.x In conclusion, our data demonstrated that obovatol prevented memory impairments in experimental AD models, which could be attributable to amelioration of neuroinflammation and amyloidogenesis by inhibition of NF‐κB signaling pathway and anti‐fibrillogenic activity of obovatol.© 2011 The Authors Journal of Neurochemistry© 2011 International Society for Neurochemistry (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5553267 Fri, 30 Dec 2011 05:00:00 +0100 5553267 http://www.medworm.com/index.php?rid=5553266&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07643.x AbstractThe expression pattern and property profile of the neuronal Ca2+ sensor guanylate cyclase‐activating protein 3 (zGCAP3) was studied by immunochemical approaches, biophysical methods and enzymatic assays. Using affinity purified antibodies immunoreactivity towards zGCAP3 was weakly detected in the outer and strongly in the inner segments of cone cells as well as in the outer plexiform layer, to a lesser degree also in the inner plexiform and ganglion cell layer of the zebrafish retina. This cellular distribution was independent of a dark/light cycle. Some neuronal Ca2+‐sensors are acylated (mainly myristoylated) at the amino‐terminus. Probing larval and adult stages of the developing zebrafish retina indicated that zGCAP3 was first expressed in a nonmyristoylated form, but was... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5553266 Fri, 30 Dec 2011 05:00:00 +0100 5553266 http://www.medworm.com/index.php?rid=5553268&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07641.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5553268 Thu, 29 Dec 2011 05:00:00 +0100 5553268 http://www.medworm.com/index.php?rid=5539210&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07631.x AbstractGlutamate receptor (GluR) δ1 is widely expressed in the developing forebrain, whereas GluRδ2 is selectively expressed in cerebellar Purkinje cells. Recently, we found that trans‐synaptic interaction of postsynaptic GluRδ2 and presynaptic neurexins (NRXNs) through cerebellin precursor protein (Cbln) 1 mediates excitatory synapse formation in the cerebellum. Thus, a question arises whether GluRδ1 regulates synapse formation in the forebrain. Here, we showed that the N‐terminal domain of GluRδ1 induced inhibitory presynaptic differentiation of some populations of cultured cortical neurons. When Cbln1 or Cbln2 was added to cultures, GluRδ1 expressed in HEK293T cells strongly induced inhibitory presynaptic differentiation of cultured cortical neurons. The synaptogenic activity... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5539210 Sun, 25 Dec 2011 13:23:35 +0100 5539210 http://www.medworm.com/index.php?rid=5526918&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07629.x AbstractSeveral prior investigations of Alzheimer’s disease (AD) patients have indicated naturally‐occurring autoantibodies against amyloid‐β (Aβ) species are produced. While many studies have focused on the relative concentrations or binding affinities of autoantibodies against Aβ‐related proteins in AD and aging, data regarding their functional properties are limited. It is generally believed that these antibodies act to aid in clearance of Aβ. However, as antibodies which bind to Aβ also typically bind to the parent amyloid precursor protein (APP), we reasoned that certain Aβ‐targeting autoantibodies may bind to APP thereby altering its conformation and processing. Here we show for the first time, that naturally occurring Aβ‐reactive autoantibodies isolated from AD pa... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5526918 Thu, 22 Dec 2011 13:17:03 +0100 5526918 http://www.medworm.com/index.php?rid=5621219&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07631.x In this study, we showed that the N‐terminal domain of GluRδ1 induced inhibitory presynaptic differentiation of some populations of cultured cortical neurons. When Cbln1 or Cbln2 was added to cultures, GluRδ1 expressed in HEK293T cells induced preferentially inhibitory presynaptic differentiation of cultured cortical neurons. The synaptogenic activity of GluRδ1 was suppressed by the addition of the extracellular domain of NRXN1α or NRXN1β containing splice segment 4. Cbln subtypes directly bound to the N‐terminal domain of GluRδ1. The synaptogenic activity of GluRδ1 in the presence of Cbln subtypes correlated well with their binding affinities. When transfected to cortical neurons, GluRδ1 stimulated inhibitory synapse formation in the presence of Cbln1 or Cbln2. These results t... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5621219 Thu, 22 Dec 2011 05:00:00 +0100 5621219 http://www.medworm.com/index.php?rid=5539218&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07632.x AbstractMephedrone (4‐methylmethcathinone) is a β‐ketoamphetamine with close structural analogy to substituted amphetamines and cathinone derivatives. Abuse of mephedrone has increased dramatically in recent years and has become a significant public health problem in the US and Europe. Unfortunately, very little information is available on the pharmacological and neurochemical actions of mephedrone. In light of the proven abuse potential of mephedrone and considering its similarity to methamphetamine and methcathinone, it is particularly important to know if mephedrone shares with these agents an ability to cause damage to dopamine nerve endings of the striatum. Accordingly, we treated mice with a binge‐like regimen of mephedrone (4X 20 or 40 mg/kg) and examined the striatum for evi... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5539218 Thu, 22 Dec 2011 05:00:00 +0100 5539218 http://www.medworm.com/index.php?rid=5539217&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07633.x AbstractCorticosterone–releasing hormone (CRH) and arginine vasopressin (AVP) are crucial components of the hypothalamic‐pituitary‐adrenal (HPA) axis that stimulates the release of adrenocorticotropic hormone (ACTH) from the pituitary and mediate the stress response. CRH binds to two subtypes of CRH receptors (CRH‐R1 and CRH‐R2) that are present in both central and peripheral tissues. We used the CRH‐R1 specific antagonist, antalarmin (ANT), the CRH‐R1 and CRH‐R2 peptide antagonist, astressin (AST), and the CRH‐R2 specific peptide antagonist, astressin2b (AST2b), to determine which CRH receptor is involved in the nicotine‐stimulated secretion of corticosterone. Male C57BL/6 mice were administered ANT (20 mg/kg, i.p.), AST (0.3 mg/kg, i.p.), AST2b (0.3 mg/kg, i.p.) or ve... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5539217 Thu, 22 Dec 2011 05:00:00 +0100 5539217 http://www.medworm.com/index.php?rid=5539216&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07634.x AbstractDuring pregnancy, activation of the maternal immune system results in inflammation in the foetal nervous system. The causative agents are pro‐inflammatory cytokines like interleukin‐1β (IL‐1β), produced by the foetus. Here we examine the effect of IL‐1β on the proliferation and differentiation of neural progenitor cells (NPCs) to better understand its potential effects on the developing brain. We find that the IL‐1β receptor (IL‐1R1) is expressed in the ventral mesencephalon of the developing brain. Furthermore, IL‐1R1 is expressed on Nestin‐positive, Sox‐2‐positive NPCs. IL‐1β treatment reduced the numbers of proliferating NPCs, an effect prevented by the IL‐1R1 receptor antagonist. LDH and MTT assays, and western blot analysis for cleaved Caspase‐3 ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5539216 Thu, 22 Dec 2011 05:00:00 +0100 5539216 http://www.medworm.com/index.php?rid=5539215&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07635.x AbstractParkinson’s disease (PD) is a chronic neurodegenerative movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. New therapeutic approaches aiming at delaying or reversing the neurodegenerative process are under active investigations. In this work, we found that harpagoside, an iridoid purified from the Chinese medicinal herb Scrophularia ningpoensis, could not only prevent but also rescue the dopaminergic neurodegeneration in MPTP/MPP+ intoxication with promising efficacy. Firstly, in cultured mesencephalic neurons, harpagoside significantly attenuated the loss of TH‐positive neuron numbers and the shortening of axonal length. Secondly, in a chronic MPTP mouse model, harpagoside dose‐dependently improved the loco‐motor abil... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5539215 Thu, 22 Dec 2011 05:00:00 +0100 5539215 http://www.medworm.com/index.php?rid=5539214&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07636.x In this study, the molecular mechanisms underlying the impact on brain activity of tacrine and two novel tacrine analogues (T1, T2) were approached by focusing on three aspects: i) their effects on brain cholinesterase activity; ii) perturbations on electron transport chain enzymes activities of non‐synaptic brain mitochondria; and iii) the role of mitochondrial lipidome changes induced by these compounds on mitochondrial bioenergetics. Brain effects were evaluated 18 hours after the administration of a single dose (75.6 μmoles/Kg) of tacrine or tacrine‐analogues. The three compounds promoted a significant reduction in brain acetylcholinesterase and butyrylcholinesterase activities. Additionally, tacrine was shown to be more efficient in brain acetylcholinesterase inhibition than T2 t... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5539214 Thu, 22 Dec 2011 05:00:00 +0100 5539214 http://www.medworm.com/index.php?rid=5539213&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07637.x AbstractEvidence accumulating during the past few years points to a significant role of matrix metalloproteinase 9 (MMP9) enzymatic activity in synaptic plasticity and cognitive processes. We have previously demonstrated that MMP9 is involved in receptor‐mediated α‐secretase‐like cleavage of APP in vitro, resulting in increased secretion of sAPPα, the soluble N‐terminal product of the non‐amyloidogenic pathway known to be involved in neuronal plasticity and memory formation. In order to study the in vivo role of MMP9, we have generated transgenic mice over‐expressing MMP9 in the brain. Herein, we demonstrate that MMP9 transgenic animals display enhanced performance in the non‐spatial novel object recognition and the spatial water‐maze task and that their enhanced performa... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5539213 Thu, 22 Dec 2011 05:00:00 +0100 5539213 http://www.medworm.com/index.php?rid=5539212&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07638.x This article is a US Government work and is in the public domain in the USA (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5539212 Thu, 22 Dec 2011 05:00:00 +0100 5539212 http://www.medworm.com/index.php?rid=5539211&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07639.x We report that axon growth is enhanced while axon and dendrite diameter are reduced following neuroserpin treatment of hippocampal neurons. More complex effects are seen on dendritic growth and branching with neuroserpin stimulating dendritic growth and branching in young neurons but switching to an inhibitory response in older neurons. The protease inhibitory activity of neuroserpin is not required to activate changes in neuronal morphology and a proportion of responses are modulated by an antagonist to the LRP1 receptor. Collectively, these findings support a key role for neuroserpin as a regulator of neuronal development through a non‐inhibitory mechanism and suggest a basis for neuroserpin’s effects on complex emotional behaviours and recent link to schizophrenia.© 2011 The Author... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5539211 Thu, 22 Dec 2011 05:00:00 +0100 5539211 http://www.medworm.com/index.php?rid=5516313&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07626.x AbstractL1CAM, an adhesion/signaling protein encoded by a gene target of the transcription repressor REST, is expressed in two alternatively spliced isoforms. The full‐length isoform, typical of low‐REST neural cells, plays key roles in survival/migration, outgrowth/fasciculation/regeneration of axons, synaptic plasticity; the isoform missing two mini‐exons, abundant in a few high‐REST non‐neural cells, maintains some effect on migration and proliferation. To investigate whether and how L1CAM alternative splicing depends on REST we used neural cell models expressing low or high levels of REST (PC12, SH‐SY5Y, differentiated NT2/D1 and primary neurons transduced or not with REST). The short isoform was found to raise when the low‐REST levels of neural cells were experimentally ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5516313 Mon, 19 Dec 2011 13:13:00 +0100 5516313 http://www.medworm.com/index.php?rid=5526922&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07603.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5526922 Mon, 19 Dec 2011 05:00:00 +0100 5526922 http://www.medworm.com/index.php?rid=5526920&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07628.x AbstractTo examine mechanisms underlying substance P (SP) release from primary sensory neurons in response to activation of the nonselective cation channel transient receptor potential ankyrin 1 (TRPA1), SP release from cultured rat dorsal root ganglion (DRG) neurons was measured, using radioimmunoassay, by stimulating TRPA1 with allyl isothiocyanate (AITC), a TRPA1 agonist. AITC‐evoked SP release occurred in a concentration‐ and time‐dependent manner. Interestingly, p38 MAP kinase (p38) inhibitor SB203580 significantly attenuated AITC‐evoked SP release. The in vivo effect of AITC‐evoked SP release from primary sensory neurons in mice was evaluated. Hind paw intraplantar injection of AITC induced nociceptive behaviors and inflammation (edema, thermal hyperalgesia). AITC‐induced... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5526920 Mon, 19 Dec 2011 05:00:00 +0100 5526920 http://www.medworm.com/index.php?rid=5526919&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07630.x AbstractMicroglia are the resident immune cells within the brain and their production of immune molecules such as cytokines and chemokines is critical for the processes of normal brain development including neurogenesis, axonal migration, synapse formation, and programmed cell death. Notably, sex differences exist in many of these processes throughout brain development; however, it is unknown whether a sex difference concurrently exists in the colonization, number, or morphology of microglia within the developing brain. We demonstrate for the first time that the number and morphology of microglia throughout development is dependent upon the sex and age of the individual, as well as the brain region of interest. Males have overall more microglia early in postnatal development (postnatal day... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5526919 Mon, 19 Dec 2011 05:00:00 +0100 5526919 http://www.medworm.com/index.php?rid=5506703&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07546.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5506703 Fri, 16 Dec 2011 13:27:16 +0100 5506703 http://www.medworm.com/index.php?rid=5506698&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07624.x In this study, the large‐scale miRNA microarrays and bioinformatics analysis were used to determine the differentially expressed miRNAs and their PKC‐isoform specific gene network in mouse brain after HPC and 6 h middle cerebral artery occlusion (MCAO). We found 4 up‐regulated and 13 down‐regulated miRNAs in the cortex of HPC mice, 26 increased and 39 decreased gene expressions of miRNAs in the peri‐infarct region of 6 h MCAO mice, and 11 up‐regulated and 22 down‐regulated miRNAs in the peri‐infarct region of HPC and 6 h MCAO mice. Based on Diff Score, 19 differentially expressed miRNAs were identified in HPC and 6 h MCAO mouse brain. Then the miRNA‐gene‐network of 19 specified miRNAs target genes of cPKCβII, γ and nPKCε‐interacting protein was predicted by using b... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5506698 Fri, 16 Dec 2011 13:24:41 +0100 5506698 http://www.medworm.com/index.php?rid=5516314&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07625.x AbstractEndocannabinoids are neuromodulatory lipids that mediate the central and peripheral neural functions. Endocannabinoids have demonstrated their anti‐proliferative, anti‐angiogenic and pro‐apoptotic properties in a series of studies. In the present study, we investigated the levels of two major endocannabinoids, anandamide and 2‐arachidonylglycerol (2‐AG), and their receptors, CB1 and CB2, in human low grade glioma (WHO grade I‐II) tissues, high grade glioma (WHO grade III‐IV) tissues, and non‐tumor brain tissue controls. We also measured the expressions and activities of the enzymes responsible for anandamide and 2‐AG biosynthesis and degradation, i.e., N‐acylphosphatidylethanolamine‐hydrolysing phospholipase D (NAPE‐PLD), fatty acid amide hydrolase (FAAH), m... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5516314 Fri, 16 Dec 2011 05:00:00 +0100 5516314 http://www.medworm.com/index.php?rid=5621221&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07623.x J. Neurochem. (2012) 10.1111/j.1471‐4159.2011.07623.xAbstractβ‐Site APP‐cleaving enzyme (BACE1) cleaves the amyloid precursor protein (APP) at the β‐secretase site to initiate the production of Aβ peptides. These accumulate to form toxic oligomers and the amyloid plaques associated with Alzheimer’s disease (AD). An increase of BACE1 levels in the brain of AD patients has been mostly attributed to alterations of its intracellular trafficking. Golgi‐associated adaptor proteins, GGA sort BACE1 for export to the endosomal compartment, which is the major cellular site of BACE1 activity. BACE1 undergoes recycling between endosome, trans‐Golgi network (TGN), and the plasma membrane, from where it is endocytosed and either further recycled or retrieved to the endosome. Phosphoryla... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5621221 Thu, 15 Dec 2011 05:00:00 +0100 5621221 http://www.medworm.com/index.php?rid=5621220&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07624.x In this study, the large‐scale miRNA microarrays and bioinformatics analysis were used to determine the differentially expressed miRNAs and their PKC‐isoform specific gene network in mouse brain after HPC and 6 h middle cerebral artery occlusion (MCAO). We found 4 up‐regulated and 13 down‐regulated miRNAs in the cortex of HPC mice, 26 increased and 39 decreased gene expressions of miRNAs in the peri‐infarct region of 6 h MCAO mice, and 11 up‐regulated and 22 down‐regulated miRNAs in the peri‐infarct region of HPC and 6 h MCAO mice. Based on Diff Score, 19 differentially expressed miRNAs were identified in HPC and 6 h MCAO mouse brain. Then the miRNA‐gene‐network of 19 specified miRNAs target genes of cPKCβII, γ and nPKCε‐interacting protein was predicted by... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5621220 Thu, 15 Dec 2011 05:00:00 +0100 5621220 http://www.medworm.com/index.php?rid=5506699&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07623.x AbstractBACE1 cleaves the amyloid precursor protein (APP) at the β‐secretase site to initiate the production of Aβ peptides. These accumulate to form toxic oligomers and the amyloid plaques associated with Alzheimer’s disease (AD). An increase of BACE1 levels in the brain of AD patients has been mostly attributed to alterations of its intracellular trafficking. Golgi‐associated adaptor proteins, GGA sort BACE1 for export to the endosomal compartment, which is its major cellular site of BACE1 activity. BACE1 undergoes recycling between endosome, trans‐Golgi network (TGN), and the plasma membrane, from where it is endocytosed and either further recycled or retrieved to the endosome. Phosphorylation of Ser498 facilitates BACE1 recognition by GGA1 for retrieval to the endosome. Ubiqu... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5506699 Thu, 15 Dec 2011 05:00:00 +0100 5506699 http://www.medworm.com/index.php?rid=5506701&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07622.x AbstractIn a retinal ischemic ex vivo model, we have reported protective effects of somatostatin (SRIF) receptor 2 (sst2). Since an ischemic condition not only causes cell death but also induces a vascular response, we asked whether vascular endothelial growth factor (VEGF) is altered in this model and whether its expression, release or localization are affected by sst2 activation. Ex vivo retinas of wild type (WT) and sst1 KO mice (which over‐express sst2) were incubated in ischemic conditions with SRIF, octreotide (OCT) or a VEGF trap. Ischemia in WT retinas caused increase of VEGF release and decrease of VEGF mRNA. Both effects were counteracted by SRIF or OCT. VEGF immunoreactivity was in retinal neurons and scarcely in vessels. Ischemia caused a significant shift of VEGF immunoreact... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5506701 Tue, 13 Dec 2011 05:00:00 +0100 5506701 http://www.medworm.com/index.php?rid=5506700&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07621.x AbstractGABAergic transmission in the neostriatum plays a central role in motor coordination, in which a plethora of GABA‐A receptor subunits combine to coordinate neural inhibition. GABAρ receptors were originally described in the mammalian retina. These receptors possess special electrophysiological and pharmacological properties, forming a characteristic class of ionotropic receptors. In previous studies, we suggested that GABAρ receptors are expressed in the neostriatum, and in this report we show that they are indeed present in all the calretinin‐positive interneurons of the neostriatum. In addition, they are located in calbindin‐positive interneurons and projection neurons that express the Dopamine D2 receptor. GABAρ receptors were also located in 30% of the GFAP‐positive ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5506700 Tue, 13 Dec 2011 05:00:00 +0100 5506700 http://www.medworm.com/index.php?rid=5621222&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07620.x We examined whether activation of these receptors would alter methamphetamine‐induced behaviour and gene expression. Mu opioid receptor activation intensified methamphetamine‐induced stereotypy and gene expression in the striatum, indicating that the mu opioid system can enhance the behavioural and genomic responses to methamphetamine. (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5621222 Thu, 08 Dec 2011 05:00:00 +0100 5621222 http://www.medworm.com/index.php?rid=5621223&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07618.x J. Neurochem. (2012) 10.1111/j.1471‐4159.2011.07618.xAbstractExposure to psychostimulants results in neuroadaptive changes of the mesencephalic dopaminergic system including morphological reorganization of dopaminergic neurons. Increased dendrite arborization and soma area were previously observed in primary cultures of mesencephalic dopaminergic neurons after 3‐day exposure to dopamine agonists via activation of D3 autoreceptors (D3R). In this work, we showed that cocaine significantly increased dendritic arborization and soma area of dopaminergic neurons from E12.5 mouse embryos by activating phosphorylation of extracellular signal‐regulated kinase (ERK) and thymoma viral proto‐oncogene (Akt). These effects were dependent on functional D3R expression because cocaine did not produ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5621223 Wed, 07 Dec 2011 05:00:00 +0100 5621223 http://www.medworm.com/index.php?rid=5488460&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07602.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5488460 Wed, 07 Dec 2011 05:00:00 +0100 5488460 http://www.medworm.com/index.php?rid=5488459&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07584.x J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07584.xAbstractAmyloid peptide (Aβ) is derived from the cleavage of amyloid precursor protein (APP), which also generates the soluble peptide APPβ (sAPPβ). An antagonist and major APP metabolic pathway involves cleavage by alpha secretase, which releases sAPPα. Although soluble Aβ oligomers are neurotoxic, Aβ monomers share similar properties with sAPPα. These include neurotrophic and neuroprotective effects, as well as stimulation of neural‐progenitor proliferation. The properties of Aβ monomers and the neurotrophic capacity of sAPPβ to stimulate axonal outgrowth suggest that Aβ production is not deleterious per se. Consequently, therapeutic strategies for Alzheimer’s disease that are targeted at Aβ‐cleaving enzymes should m... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5488459 Wed, 07 Dec 2011 05:00:00 +0100 5488459 http://www.medworm.com/index.php?rid=5488458&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07586.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5488458 Wed, 07 Dec 2011 05:00:00 +0100 5488458 http://www.medworm.com/index.php?rid=5477939&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07616.x AbstractRecent evidence indicates that supplementation with a specific combination of nutrients may affect cell membrane synthesis and composition. In order to investigate whether such nutrients may also modify the physical properties of membranes, and affect membrane‐bound processes involved in signal transduction pathways, we studied the effects of nutrient supplementation on G protein‐coupled receptor (GPCR) activation in vitro. In particular, we investigated muscarinic receptors, which are important for the progression of memory deterioration and pathology of Alzheimer’s disease. Nerve Growth Factor (NGF) differentiated pheochromocytoma cells (PC12) that were supplemented with specific combinations of nutrients showed enhanced responses to muscarinic receptor agonists in a membra... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5477939 Wed, 07 Dec 2011 05:00:00 +0100 5477939 http://www.medworm.com/index.php?rid=5477938&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07618.x AbstractExposure to psychostimulants results in neuroadaptive changes of the mesencephalic dopaminergic system including morphological reorganization of dopaminergic neurons. Increased dendrite arborization and soma area were previously observed in primary cultures of mesencephalic dopaminergic neurons after 3‐day exposure to dopamine agonists via activation of D3 autoreceptors (D3R). In this work we showed that cocaine significantly increased dendritic arborization and soma area of dopaminergic neurons from E12.5 mouse embryos by activating phosphorylation of extracellular signal‐regulated kinase (ERK) and thymoma viral proto‐oncogene (Akt). These effects were dependent on functional D3R expression since cocaine did not produce morphological changes or ERK/Akt phosphorylation neithe... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5477938 Wed, 07 Dec 2011 05:00:00 +0100 5477938 http://www.medworm.com/index.php?rid=5477937&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07617.x AbstractObesity can be associated with systemic low‐grade inflammation that contributes to obesity‐related metabolic disorders. Recent studies raise the possibility that hypothalamic inflammation contributes to the pathogenesis of diet‐induced obesity (DIO), while another study reported that obesity decreases the expression of pro‐inflammatory cytokines in spleen. The following study examines the hypothesis that obesity suppresses the splenic synthesis of the anti‐inflammatory cytokine, interleukin (IL)‐10, thereby resulting in chronic hypothalamic inflammation. The results showed that due to oxidative stress or apoptosis, the synthesis of splenic IL‐10 was decreased in DIO when compared with non‐obesity rats. Splenectomy (SPX) accelerated DIO‐induced inflammatory respons... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5477937 Wed, 07 Dec 2011 05:00:00 +0100 5477937 http://www.medworm.com/index.php?rid=5477945&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07610.x Astrocytes respond to trauma by stimulating inflammatory signaling. In studies of cerebral ischemia and spinal cord injury, astrocytic signaling is mediated by the cytokine receptor glycoprotein 130 (gp130) and Janus kinase (Jak) which phosphorylates the transcription factor signal transducer and activator of transcription‐3 (STAT3). To determine if STAT3 is activated after traumatic brain injury (TBI), adult male Sprague Dawley rats received moderate parasagittal fluid‐percussion brain injury or sham surgery, and then the ipsilateral cortex and hippocampus were analyzed at various post‐traumatic time periods for up to 7 days. Western blot analyses indicated that STAT3 phosphorylation significantly increased at 30 min and lasted for 24 hr post‐TBI. A significant increase in gp130 a... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5477945 Tue, 06 Dec 2011 05:00:00 +0100 5477945 http://www.medworm.com/index.php?rid=5477944&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07612.x AbstractS100B is a calcium‐binding protein concentrated in glial cells, although it has also been detected in definite extra‐neural cell types. Its biological role is still debated. When secreted, S100B is believed to have paracrine/autocrine trophic effects at physiological concentrations, but toxic effects at higher concentrations. Elevated S100B levels in biological fluids (cerebrospinal fluid, blood, urine, saliva, amniotic fluid) are thus regarded as a biomarker of pathological conditions, including perinatal brain distress, acute brain injury, brain tumors, neuroinflammatory/neurodegenerative disorders, psychiatric disorders. In the majority of these conditions high S100B levels offer an indicator of cell damage when standard diagnostic procedures are still silent. The key questi... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5477944 Tue, 06 Dec 2011 05:00:00 +0100 5477944 http://www.medworm.com/index.php?rid=5477943&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07611.x AbstractThe regulation of presynaptic glutamate release is important in the maintenance and fidelity of excitatory transmission in the nervous system. Here we report a novel interaction between a ligand‐gated ion channel and a G‐protein coupled receptor which regulates glutamate release from parallel fiber axon terminals. Immunocytochemical analysis revealed that GABAA receptors and the high affinity Group III metabotropic glutamate receptor subtype 4 (mGlu4) are co‐localized on glutamatergic parallel fiber axon terminals in the cerebellum. GABAA and mGlu4 receptors were also found to co‐immunoprecipitate from cerebellar membranes. Independently, these two receptors have opposing roles on glutamate release: presynaptic GABAA receptors promote, while mGlu4 receptors inhibit, glutama... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5477943 Tue, 06 Dec 2011 05:00:00 +0100 5477943 http://www.medworm.com/index.php?rid=5477942&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07613.x AbstractThe physiological function of the cellular prion protein (PrPC) and its conversion into its infectious form (PrPSc) are central issues to understanding the pathogenesis of prion diseases. The N‐terminal moiety of PrPC (NH2‐PrPC) is an unstructured region with the characteristic of interacting with a broad range of partners. These interactions endow PrPC with multifunctional and sometimes contrasting capabilities, including neuroprotection and neurotoxicity. Recently, binding of β‐sheet rich conformers to NH2‐PrPC demonstrated a probable neurotoxic function for PrPC in Alzheimer’s disease. NH2‐PrPC also enhances the propagation of prions in vivo and is the target of the most potent antiprion compounds. Another level of complexity is provided by endoproteolysis and relea... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5477942 Tue, 06 Dec 2011 05:00:00 +0100 5477942 http://www.medworm.com/index.php?rid=5477941&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07614.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5477941 Tue, 06 Dec 2011 05:00:00 +0100 5477941 http://www.medworm.com/index.php?rid=5477940&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07615.x AbstractThe microtubule‐associated STOP (also known as MAP6) protein plays a key role in neuron architecture and synaptic plasticity, the dysfunctions of which are thought to be implicated in the pathophysiology of psychiatric diseases. The deletion of STOP in mice leads to severe disorders reminiscent of several schizophrenia‐like symptoms, which are also associated with differential alterations of the serotonergic tone in somas versus terminals. In STOP knockout (KO) compared to wild‐type mice, serotonin (5‐HT) markers are found to be markedly accumulated in the raphe nuclei and, in contrast, deeply depleted in all serotonergic projection areas. In the present study, we carefully examined whether the 5‐HT imbalance would lead to behavioral consequences evocative of mood and/or ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5477940 Tue, 06 Dec 2011 05:00:00 +0100 5477940 http://www.medworm.com/index.php?rid=5573020&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07608.x In this study, we demonstrated that deficits in cognitive functions in MPTP‐treated mice were associated with reduced calcium/calmodulin‐dependent protein kinase II (CaMKII) autophosphorylation and impaired long‐term potentiation (LTP) induction in the hippocampal CA1 region. Mice were injected once a day for 5 days with MPTP (25 mg/kg i.p.). The impaired motor coordination was observed 1 or 2 week after MPTP treatment as assessed by rota‐rod and beam‐walking tasks. In immunoblotting analyses, the levels of tyrosine hydroxylase protein and CaMKII autophosphorylation in the striatum were significantly decreased 1 week after MPTP treatment. By contrast, deficits of cognitive functions were observed 3–4 weeks after MPTP treatment as assessed by novel object recognition a... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5573020 Fri, 02 Dec 2011 05:00:00 +0100 5573020 http://www.medworm.com/index.php?rid=5488449&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07620.x AbstractMu opioid receptors are densely expressed in the patch compartment of striatum and contribute to methamphetamine‐induced patch‐enhanced gene expression and stereotypy. In order to further elucidate the role of mu opioid receptor activation in these phenomena, we examined whether activation of mu opioid receptors would enhance methamphetamine‐induced stereotypy and prodynorphin, c‐fos, arc and zif/268 expression in the patch and/or matrix compartments of striatum, as well as the impact of mu opioid receptor activation on the relationship between patch‐enhanced gene expression and stereotypy. Male Sprague‐Dawley rats were intrastriatally infused with D‐Ala(2)‐N‐Me‐Phe(4),Gly(5)‐ol]enkephalin (DAMGO; 1 μg/μl), treated with methamphetamine (0.5 mg/kg) and sacrif... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5488449 Thu, 01 Dec 2011 05:00:00 +0100 5488449 http://www.medworm.com/index.php?rid=5477936&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07619.x AbstractNogo‐66 is a 66‐amino‐acid‐residue extracellular domain of Nogo‐A, which plays a key role in inhibition neurite outgrowth of central nervous system through binding to the Nogo‐66 receptor (NgR) expressed on the neuron. Recent studies have confirmed that NgR is also expressed on the surface of macrophages/microglia in multiple sclerosis, but its biological effects remain unknown. In the present study, our results demonstrated that Nogo‐66 triggered microglia anti‐adhesion and inhibited their migration in vitro, which was mediated by NgR. We also assessed the roles of small GTP (glycosyl phosphatidylinositol)‐binding proteins of the Rho family as the downstream signal transducers on the microglia adhesion and mobility induced by Nogo‐66. The results showed that No... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5477936 Thu, 01 Dec 2011 05:00:00 +0100 5477936 http://www.medworm.com/index.php?rid=5470258&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07608.x AbstractParkinson’s disease (PD) patients frequently reveal deficit in cognitive functions during the early stage in PD. The dopaminergic neurotoxin, 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine (MPTP)‐induced neurodegeneration causes an injury of the basal ganglia and is associated with PD‐like behaviors. Here we demonstrated that deficits in cognitive functions in MPTP‐treated mice were associated with reduced calcium/calmodulin‐dependent protein kinase II (CaMKII) autophosphorylation and impaired LTP induction in the hippocampal CA1 region. Mice were injected once a day for 5 days with MPTP (25 mg/kg i.p.). The impaired motor coordination was observed 1 or 2 week after MPTP treatment as assessed by rota‐rod and beam‐walking tasks. In immunoblotting analyses, t... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5470258 Thu, 01 Dec 2011 05:00:00 +0100 5470258 http://www.medworm.com/index.php?rid=5459476&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07606.x AbstractDocosahexaenoic acid (DHA) has neuroprotective effects in several neurodegenerative disease conditions. However, the underlying mechanisms are not well understood. In the present study, we investigated the effects of DHA on astrocyte Ca2+ signaling under in vitro ischemic conditions (oxygen/glucose deprivation and reoxygenation, OGD/REOX). OGD (2 hour) triggered a Ca2+ER store overload (∼ 1.9 fold). Ca2+ uptake by the Ca2+ER stores was further augmented during REOX and Ca2+ER was elevated by ∼ 4.7‐fold at 90 min REOX. Interestingly, Ca2+ER stores abruptly released Ca2+ at ∼ 120 min REOX and emptied at 160 min REOX. Depletion of Ca2+ER stores led to delayed elevation of intracellular Ca2+ concentration (Ca2+cyt) and cell death. Activation of the purinergic receptor P2Y1 was ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459476 Thu, 01 Dec 2011 05:00:00 +0100 5459476 http://www.medworm.com/index.php?rid=5450245&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07604.x AbstractCbln1 is the prototype of a family of secreted neuronal glycoproteins (Cbln1‐4) and its genetic elimination results in synaptic alterations in cerebellum and striatum. In cerebellum, Cbln1 acts as a bi‐functional ligand bridging pre‐synaptic β‐neurexins on granule cells to post‐synaptic Grid2 on Purkinje neurons. Although much is known concerning the action of Cbln1, little is known of the function of its other family members. Here we show that Cbln1 and Cbln2 have similar binding activities to β‐neurexins and Grid2 and the targeted ectopic expression of Cbln2 to Purkinje cells in transgenic mice rescues the cerebellar deficits in Cbln1‐null animals: suggesting the two proteins have redundant function mediated by their common receptor binding properties. Cbln1 and C... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5450245 Mon, 28 Nov 2011 13:32:23 +0100 5450245 http://www.medworm.com/index.php?rid=5459495&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07475.x In this study, we review the mechanisms by which AICD is generated and how its production is regulated. Furthermore, we discuss the degradation mechanism underlying its rapid catabolic fate. Finally, we review putative AICD‐related functions and more particularly, the numerous studies indicating that AICD could translocate to the nucleus and control at a transcriptional level, the expression of a series of proteins involved in various functions including the control of cell death and Aβ degradation. (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459495 Mon, 28 Nov 2011 05:00:00 +0100 5459495 http://www.medworm.com/index.php?rid=5459494&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07476.x J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07476.xAbstractβ‐Secretase (memapsin 2; BACE‐1) is the first protease in the processing of amyloid precursor protein leading to the production of amyloid‐β (Aβ) in the brain. It is believed that high levels of brain Aβ are responsible for the pathogenesis of Alzheimer’s disease (AD). Therefore, β‐secretase is a major therapeutic target for the development of inhibitor drugs. During the past decade, steady progress has been made in the evolution of β‐secretase inhibitors toward better drug properties. Recent inhibitors are potent, selective and have been shown to penetrate the blood‐brain barrier to inhibit Aβ levels in the brains of experimental animals. Moreover, continuous administration of a β‐secretase inhibitor wa... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459494 Mon, 28 Nov 2011 05:00:00 +0100 5459494 http://www.medworm.com/index.php?rid=5459493&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07477.x J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07477.xAbsract‘Secretase’ is a generic term coined more than 20 years ago to refer to a group of proteases responsible for the cleavage of a vast number of membrane proteins. These endoproteolytic events result in the extracellular or intracellular release of soluble metabolites associated with a broad range of intrinsic physiological functions. α‐Secretase refers to the activity targeting the amyloid precursor protein (APP) and generating sAPPα, a soluble extracellular fragment potentially associated with neurotrophic and neuroprotective functions. Several proteases from the a disintegrin and metalloproteinase (ADAM) family, including ADAM10 and ADAM17, have been directly or indirectly associated with the constitutive and regul... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459493 Mon, 28 Nov 2011 05:00:00 +0100 5459493 http://www.medworm.com/index.php?rid=5459492&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07478.x J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07478.xAbstractFor nearly 100 years following the first description of this neurological disorder by Dr Alois Alzheimer, amyloid plaques and neurofibrillary tangles have been hypothesized to cause neuronal loss. With evidence that the extent of insoluble, deposited amyloid poorly correlated with cognitive impairment, research efforts focused on soluble forms of Aβ, also referred as Aβ oligomers. Following a decade of studies, soluble oligomeric forms of Aβ are now believed to induce the deleterious cascade(s) involved in the pathophysiology of Alzheimer’s disease. In this review, we will discuss our current understanding about endogenous oligomeric Aβ production, their relative toxicity in vivo and in vitro, and explore the potential ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459492 Mon, 28 Nov 2011 05:00:00 +0100 5459492 http://www.medworm.com/index.php?rid=5459491&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07501.x J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07501.xAbstractγ‐Secretase is a membrane embedded aspartyl protease complex with presenilin as the catalytic component. Along with β‐secretase, this enzyme produces the amyloid β‐protein of Alzheimer’s disease (AD) from the amyloid β‐protein precursor. Because of its key role in the pathogenesis of AD, γ‐secretase has been a prime target for drug discovery, and many inhibitors of this protease have been developed. The therapeutic potential of these inhibitors is virtually negated by the fact that γ‐secretase is an essential part of the Notch signaling pathway, rendering the compounds unacceptably toxic upon chronic exposure. However, these compounds have served as useful chemical tools for biological investigations. In con... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459491 Mon, 28 Nov 2011 05:00:00 +0100 5459491 http://www.medworm.com/index.php?rid=5459490&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07500.x J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07500.xAbstractThe biggest risk factor for Alzheimer’s disease is the process of ageing, but the mechanisms that lead to the manifestation of the disease remain to be elucidated. Why age triggers the disease is unclear but an emerging theme is the inability for a cell to efficiently maintain many key processes such as energy production, repair, and regenerative mechanisms. Metal ions are essential to the metabolic function of every cell. This review will explore the role and reported changes in metal ions in Alzheimer disease, particularly the brain, blood and cerebral spinal fluid, emphasizing how iron, copper and zinc may be involved through the interactions with amyloid precursor protein, the proteolytically cleaved peptide amyloid‐bet... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459490 Mon, 28 Nov 2011 05:00:00 +0100 5459490 http://www.medworm.com/index.php?rid=5459489&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07505.x J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07505.xAbstractThe presenilin complex is composed of four core proteins (presenilin 1 or presenilin 2, APH1, nicastrin, and PEN2). Several endogenous proteins have been reported to selectively modulate the function of the presenilin complexes; these include transmembrane trafficking protein, 21‐KD (TMP21), CD147 antigen (basigin), the γ‐secretase‐activating protein (gSAP), and the orphan G‐protein‐coupled receptor 3. Because the structure and assembly of these complexes underlies their activity, this review will discuss current work on the assembly of the complex and on presenilin‐interacting proteins that regulate secretase activity. (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459489 Mon, 28 Nov 2011 05:00:00 +0100 5459489 http://www.medworm.com/index.php?rid=5459488&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07507.x J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07507.xAbstractThe prescribed drugs for treatment of cognitive deficits in Alzheimer’s disease (AD) patients are regarded as symptomatic drugs. Effective disease modifying therapies are not yet prescribed in AD patients. Three major hallmarks of AD (e.g. cholinergic hypofunction, Aβ and tau neuropathologies) are closely linked raising the expectation that restoring the cholinergic hypofunction to normal, in particular via selective activation of M1 muscarinic receptors, may alter the onset or progression of AD dementia. This review is focused mainly on modulation of amyloid precursor processing and Aβ levels in the brain via cholinergic treatment strategies based on M1 muscarinic agonists versus other cholinergic treatments (e.g. cholines... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459488 Mon, 28 Nov 2011 05:00:00 +0100 5459488 http://www.medworm.com/index.php?rid=5459487&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07506.x In this study, we review recent advances in the study of the molecular and cellular mechanisms underlying Alzheimer’s disease‐associated synaptic dysfunction and memory deficits, and how these mechanisms could provide novel avenues for therapeutic intervention to treat this devastating neurodegenerative disease. (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459487 Mon, 28 Nov 2011 05:00:00 +0100 5459487 http://www.medworm.com/index.php?rid=5459486&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07510.x J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07510.xAbstractThe amyloid cascade hypothesis of Alzheimer’s disease envisages that the initial elevation of amyloid β‐peptide (Aβ) levels, especially of Aβ1‐42, is the primary trigger for the neuronal cell death specific to onset of Alzheimer’s disease. There is now substantial evidence that brain amyloid levels are manipulable because of a dynamic equilibrium between their synthesis from the amyloid precursor protein and their removal by amyloid‐degrading enzymes (ADEs) providing a potential therapeutic strategy. Since the initial reports over a decade ago that two zinc metallopeptidases, insulin‐degrading enzyme and neprilysin (NEP), contributed to amyloid degradation in the brain, there is now an embarras de richesses in re... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459486 Mon, 28 Nov 2011 05:00:00 +0100 5459486 http://www.medworm.com/index.php?rid=5459485&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07515.x J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07515.xAbstractAlzheimer’s disease (AD) is the most common neurodegenerative disorder leading to dementia. Neuritic plaques are the hallmark neuropathology in AD brains. Proteolytic processing of amyloid‐β precursor protein at the β site by beta‐site amyloid‐β precursor protein‐cleaving enzyme 1 (BACE1) is essential to generate Aβ, a central component of the neuritic plaques. BACE1 is increased in some sporadic AD brains, and dysregulation of BACE1 gene expression plays an important role in AD pathogenesis. This review will focus on the regulation of BACE1 gene expression at the transcriptional, post‐transcriptional, translation initiation, translational and post‐translational levels, and its role in AD pathogenesis. Further... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459485 Mon, 28 Nov 2011 05:00:00 +0100 5459485 http://www.medworm.com/index.php?rid=5459484&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07512.x In this study, we review the identification and basic characteristics of BACE1, as well as the progress in our understanding of BACE1 cell biology, substrates, and phenotypes of BACE1 knockout mice that are informative about the physiological functions of BACE1 beyond amyloid precursor protein cleavage. These data are crucial for predicting potential mechanism‐based toxicity that would arise from inhibiting BACE1 for the treatment or prevention of AD. (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459484 Mon, 28 Nov 2011 05:00:00 +0100 5459484 http://www.medworm.com/index.php?rid=5459483&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07575.x In this study, we review our finding of APP mutations in Alzheimer’s disease in 1990–1991 with the benefit of 20 years’ perspective. We discuss the historical context in which we made the finding, its immediate and continuing effects on research activity and our hopes for successful clinical testing of the hypothesis. We also briefly discuss the effects finding APP mutations has had on our own careers and those of our colleagues from 1991. (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459483 Mon, 28 Nov 2011 05:00:00 +0100 5459483 http://www.medworm.com/index.php?rid=5459482&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07519.x J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07519.xAbstractβ‐Amyloid precursor protein (APP) is a critical factor in the pathogenesis of Alzheimer’s disease (AD). APP undergoes post‐translational proteolysis/processing to generate the hydrophobic β‐amyloid (Aβ) peptides. Deposition of Aβ in the brain, forming oligomeric Aβ and plaques, is identified as one of the key pathological hallmarks of AD. The processing of APP to generate Aβ is executed by β‐ and γ‐secretase and is highly regulated. Aβ toxicity can lead to synaptic dysfunction, neuronal cell death, impaired learning/memory and abnormal behaviors in AD models in vitro and in vivo. Aside from Aβ, proteolytic cleavages of APP can also give rise to the APP intracellular domain, reportedly involved in multiple ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459482 Mon, 28 Nov 2011 05:00:00 +0100 5459482 http://www.medworm.com/index.php?rid=5459477&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07605.x We report a seizure triggers a rapid (< 2 hrs) decrease of EPSC‐like current‐induced phasic firing associated with increased transient A‐type K+ current. Seizures also rapidly redistributed the A‐type K+ channel subunit Kv4.2 to the neuronal surface implicating a molecular substrate for the increased K+ current. Glutamate applied in vitro mimicked the effect, suggesting a direct effect of glutamatergic transmission. Importantly, LGI1, a secreted synaptic protein mutated to cause human partial epilepsy, regulated this seizure‐induced circuit response. Human epilepsy‐associated dominant negative truncated mutant LGI1 inhibited the seizure‐induced suppression of phasic firing, increase of A‐type K+ current, and recruitment of Kv4.2 surface expression (in vivo and in vitro).... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459477 Mon, 28 Nov 2011 05:00:00 +0100 5459477 http://www.medworm.com/index.php?rid=5442949&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07601.x AbstractD‐serine is an endogenous neurotransmitter that binds to the NMDA receptor, thereby increasing the affinity for glutamate, and the potential for excitotoxicity. The primary source of D‐serine in vivo is enzymatic racemization by serine racemase (SR). Regulation of D‐serine in vivo is poorly understood, but is thought to involve a combination of controlled production, synaptic reuptake by transporters, and intracellular degradation by D‐amino acid oxidase (DAO). However, SR itself possesses a well‐characterized eliminase activity which effectively degrades D‐serine as well. D‐serine is increased two‐fold in spinal cords of G93A SOD1 mice – the standard model of amyotrophic lateral sclerosis (ALS). ALS mice with SR disruption show earlier symptom onset, but survive ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5442949 Fri, 25 Nov 2011 13:22:49 +0100 5442949 http://www.medworm.com/index.php?rid=5561946&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07601.x J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07601.xAbstractd‐Serine is an endogenous neurotransmitter that binds to the NMDA receptor, thereby increasing the affinity for glutamate, and the potential for excitotoxicity. The primary source of d‐serine in vivo is enzymatic racemization by serine racemase (SR). Regulation of d‐serine in vivo is poorly understood, but is thought to involve a combination of controlled production, synaptic reuptake by transporters, and intracellular degradation by d‐amino acid oxidase (DAO). However, SR itself possesses a well‐characterized eliminase activity, which effectively degrades d‐serine as well. d‐Serine is increased two‐fold in spinal cords of G93A Cu,Zn‐superoxide dismutase (SOD1) mice – the standard model of amyotrophic latera... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5561946 Fri, 25 Nov 2011 05:00:00 +0100 5561946 http://www.medworm.com/index.php?rid=5450252&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07591.x AbstractSpontaneous electrical network activity plays a major role in the control of cell survival in the developing brain. Several intracellular pathways are implicated in transducing electrical activity into gene expression dependent and independent survival signals. These include activation of Phosphatidylinositol 3‐kinase (PI3K) and its downstream effector Akt, activation of Ras and subsequently MAPK/ERK (MEK) and extracellular signal‐regulated kinase (ERK) and signalling via Calcium/Calmodulin dependent protein kinase (CaMK). In the present study we analyzed the role of these pathways for the control of neuronal survival in different extracellular potassium concentrations ([K+]ex). Organotypic neocortical slice cultures prepared from newborn mice were kept in 5.3, 8.0 and 25.0 mM ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5450252 Fri, 25 Nov 2011 05:00:00 +0100 5450252 http://www.medworm.com/index.php?rid=5450251&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07592.x We examined the role of nectin‐1 ectodomain shedding on synaptogenesis in cultured rat hippocampal neurons. Nectins are Ca2+‐independent immunoglobulin‐like adhesion molecules, involved in cell‐cell adherens junctions (AJs). Herein, we show that the processing of nectin‐1 occurs by multiple endoproteolytic steps both in vivo and in vitro. We identified regions containing two distinct cleavage sites within the ectodomain of nectin‐1. By alanine scanning mutagenesis, two point mutations that disrupt nectin‐1 ectodomain cleavage events were identified. Expression of these mutants significantly alters the density of dendritic spines. These findings suggest that ectodomain shedding of nectin‐1 regulates dendritic spine density and related synaptic functions. (Source: Journal of ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5450251 Fri, 25 Nov 2011 05:00:00 +0100 5450251 http://www.medworm.com/index.php?rid=5450250&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07593.x We report here that a significant enhancement in apoptosis in rat cerebellar granule neurons (CGNs) was observed upon incubation with 5 mM K+/serum free (LK‐S) medium. Cholesterol enrichment further potentiated CGN apoptosis incubated under LK‐S medium. On the contrary, cholesterol depletion using MβCD protected the CGNs from apoptosis induced by LK‐S treatment. Cholesterol enrichment, however, did not induce apoptosis in CGNs that have been incubated with 25 mM K+/serum (HK+S) medium. Mechanistically, increased IK currents and DNA fragmentation were found in CGNs incubated in LK‐S, which was further potentiated in the presence of cholesterol. Cholesterol‐treated CGNs also exhibited increased cAMP levels and upregulation of Kv2.1 expression. Increased levels of activated form of... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5450250 Fri, 25 Nov 2011 05:00:00 +0100 5450250 http://www.medworm.com/index.php?rid=5450249&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07594.x AbstractActivation of microglia, the resident macrophages of the brain, around the amyloid plaques is a key hallmark of Alzheimer’s disease (AD). Recent evidence in mouse models indicates that microglia are required for the neurodegenerative process of AD. Amyloid‐β (Aβ) peptides, the core components of the amyloid plaques, can trigger microglial activation by interacting with several Toll‐like receptors (TLRs), including TLR4. Here, we show that resveratrol, a natural polyphenol associated with anti‐inflammatory effects and currently in clinical trials for AD, prevented the activation of murine RAW 264.7 macrophages and microglial BV‐2 cells treated with the TLR4 ligand, lipopolysaccharide (LPS). Resveratrol preferentially inhibited NF‐κB activation upon LPS stimulation by ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5450249 Fri, 25 Nov 2011 05:00:00 +0100 5450249 http://www.medworm.com/index.php?rid=5450248&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07595.x AbstractAstrocytes undergo rapid activation after injury, which is mediated in part by the transcription factor NF‐κB. Consequently, activated astrocytes have been shown to induce the NF‐κB regulated phagocyte NADPH oxidase (PHOX), resulting in elevated production of reactive oxygen species (ROS). We investigated the regulatory mechanisms of PHOX‐induced oxidative stress in astrocytes and its non cell‐autonomous effects on retinal ganglion cell (RGC) loss following retinal ischemia‐reperfusion (IR) injury. To study PHOX activity and neurotoxicity mediated by glial NF‐κB, we employed GFAP‐IκBα‐dn transgenic mice (TG), where the NF‐κB canonical pathway is suppressed specifically in astrocytes. Our analysis showed that NF‐κB activation in astrocytes correlated with ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5450248 Fri, 25 Nov 2011 05:00:00 +0100 5450248 http://www.medworm.com/index.php?rid=5450247&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07596.x AbstractNecrosis has long been considered accidental and uncontrolled, but during the last decade it became clear that necrosis is also a well‐orchestrated form of cell demise, being as well programmed as apoptosis. To explain the mechanism of neuronal necrosis after ischemia/reperfusion, the ‘calpain‐cathepsin hypothesis’ formulated in 1998 postulates that the postischemic μ‐calpain activation compromises integrity of the lysosomal membrane, thereby leading to cathepsin spillage. Another cause of the lysosomal rupture occurring during reperfusion is reactive oxygen species (ROS) that generate 4‐hydroxy‐2‐nonenal (HNE) by oxidation of membrane fatty acids such as linolenic and arachidonic acids. HNE is an endogenous neurotoxin, because HNE‐induced carbonylation of the su... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5450247 Fri, 25 Nov 2011 05:00:00 +0100 5450247 http://www.medworm.com/index.php?rid=5450246&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07597.x AbstractDietary n‐6 polyunsaturated fatty acid (PUFA) deprivation in rodents reduces brain arachidonic acid (20:4n‐6) concentration and 20:4n‐6‐preferring cytosolic phospholipase A2 (cPLA2‐IVA) and cyclooxygenase (COX)‐2 expression, while increasing brain docosahexaenoic acid (DHA, 22:6n‐3) concentration and DHA‐selective Ca2+‐independent iPLA2‐VIA expression. We hypothesized that these changes are accompanied by upregulated brain DHA metabolic rates. Using a fatty acid model, brain DHA concentrations and kinetics were measured in unanesthetized male rats fed, for 15 weeks post‐weaning, an n‐6 PUFA “adequate” (31.4 wt% linoleic acid) or “deficient” (2.7 wt% linoleic acid) diet, each lacking 20:4n‐6 and DHA. [1‐14C]DHA was infused intravenously, arterial ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5450246 Fri, 25 Nov 2011 05:00:00 +0100 5450246 http://www.medworm.com/index.php?rid=5442952&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07598.x Conclusion: The 8‐OHDPAT co‐treatment reversed the L‐DOPA‐induced decrease of [11C]raclopride binding and increase of extracellular DA and reduced the severity of LID. The reversal of the effect of L‐DOPA on [11C]raclopride binding, extracellular DA and LID by 5‐HT agonist administration is consistent with the notion that part of the DA increase associated with LID originates in serotonergic neurons. (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5442952 Fri, 25 Nov 2011 05:00:00 +0100 5442952 http://www.medworm.com/index.php?rid=5442951&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07599.x AbstractDuring excitotoxic neuronal death, Bax translocates to the mitochondria where it plays an important role by contributing to the release of proapoptotic factors. However, how Bax translocates to the mitochondria during excitotoxicity remains poorly understood. Herein our data suggest the presence of a novel signalling mechanism by which NMDA receptor stimulation promotes Bax translocation. This signalling pathway is triggered by dephosphorylation of cofilin. Once dephosphorylated, cofilin might interact physically with Bax acting as a carrier for it, translocating it to the mitochondria, where it contributes to mitochondrial membrane despolarization, permeabilization and to the release of apoptotic factors, thus leading to neuronal death. Lack‐of‐function studies indicate that o... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5442951 Fri, 25 Nov 2011 05:00:00 +0100 5442951 http://www.medworm.com/index.php?rid=5442950&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07600.x AbstractDuring central nervous system (CNS) development, individual oligodendrocytes myelinate multiple axons, thus requiring the outgrowth and extensive branching of oligodendroglial processes. Laminin‐deficient mice have a lower percentage of myelinated axons, which may indicate a defect in the ability to properly extend and branch processes. It remains unclear, however, to what extent extracellular matrix (ECM) receptors contribute to oligodendroglial process remodeling itself. In the current study we report that the ECM receptor dystroglycan is necessary for laminin enhancement of filopodial formation, process outgrowth, and process branching in differentiating oligodendroglia. During early oligodendroglial differentiation, the disruption of dystroglycan‐laminin interactions, via b... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5442950 Fri, 25 Nov 2011 05:00:00 +0100 5442950 http://www.medworm.com/index.php?rid=5432835&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07590.x This report reviews the recent discovery of the potential role of the chemical structure of antipsychotics in their therapeutic properties and metabolic disturbances. By developing structure‐activity relationship (SAR) studies for atypical antipsychotics, we will improve our understanding of the structural modifications of these chemical classes that lead to reduced weight gain, which will be an invaluable step toward the discovery of the next generation of atypical antipsychotics. In this review, we suggest that a novel dibenzodiazepine or thienobenzodiazepine antipsychotic drug with lower affinity for H1 receptors may significantly advance schizophrenia therapy. (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5432835 Tue, 22 Nov 2011 13:17:50 +0100 5432835 http://www.medworm.com/index.php?rid=5526921&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07588.x J. Neurochem. (2012) 10.1111/j.1471‐4159.2011.07588.xAbstractThe study of neurodegenerative disorders has had a major impact on our understanding of more fundamental mechanisms underlying neurobiology. Breakthroughs in the genetics of Alzheimer’s (AD) and Parkinson’s diseases (PD) has resulted in new knowledge in the areas of axonal transport, energy metabolism, protein trafficking/clearance and synaptic physiology. The major neurodegenerative diseases have in common a regional or network pathology associated with abnormal protein accumulation(s) and various degrees of motor or cognitive decline. In AD, β‐amyloids are deposited in extracellular diffuse and compacted plaques as well as intracellularly. There is a major contribution to the disease by the co‐existence of an intrane... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5526921 Sun, 20 Nov 2011 05:00:00 +0100 5526921 http://www.medworm.com/index.php?rid=5432837&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07588.x AbstractThe study of neurodegenerative disorders has had a major impact on our understanding of more fundamental mechanisms underlying neurobiology. Breakthroughs in the genetics of Alzheimer’s (AD) and Parkinson’s diseases (PD) has resulted in new knowledge in the areas of axonal transport, energy metabolism, protein trafficking/clearance and synaptic physiology. The major neurodegenerative diseases have in common a regional or network pathology associated with abnormal protein accumulation(s) and various degrees of motor or cognitive decline. In AD, β‐amyloids are deposited in extracellular diffuse and compacted plaques as well as intracellularly. There is a major contribution to the disease by the co‐existence of an intraneuronal tauopathy. Additionally, PD‐like Lewy Bodies (... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5432837 Sun, 20 Nov 2011 05:00:00 +0100 5432837 http://www.medworm.com/index.php?rid=5432836&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07589.x AbstractMore and more data show isoflurane, a commonly used volatile anesthetic has dual effects on neuron fate. However, the underlying mechanisms that can explain the apparent paradox are poorly understood. Hypoxia inducible factor (HIF)‐1α, a transcription factor, has been found regulating both prosurvival and prodeath pathways in the central nervous system. Previously we found isoflurane can activate HIF‐1α under normoxic conditions in vitro and HIF‐1α has been found to be involved in the preconditioning effect of isoflurane in various organs. Here, we investigated whether HIF‐1α is a contributing factor in the neurodegenration in rodent primary cultured neurons and in developing rat brain. Isoflurane dose‐dependently induced apoptotic neurodegeneration in neonatal rats a... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5432836 Sun, 20 Nov 2011 05:00:00 +0100 5432836 http://www.medworm.com/index.php?rid=5423685&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07587.x AbstractThe choroid plexus (CP) epithelium develops from the ependyma that lines the ventricular system, and plays a critical role in the development and function of the brain. In addition to being the primary site of CSF production, the CP maintains the blood‐CSF barrier via apical tight junctions between epithelial cells. Here we show that the 22‐member γ‐Protocadherin (γ‐Pcdh) family of cell adhesion molecules, which we have implicated previously in synaptogenesis and neuronal survival, is highly expressed by both CP epithelial and ependymal cells, in which γ‐Pcdh protein localization is, surprisingly, tightly restricted to the apical membrane. Multi‐label immunostaining demonstrates that γ‐Pcdhs are excluded from tight junctions, basolateral adherens junctions, and ap... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5423685 Sat, 19 Nov 2011 13:35:29 +0100 5423685 http://www.medworm.com/index.php?rid=5423686&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07585.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5423686 Thu, 17 Nov 2011 05:00:00 +0100 5423686 http://www.medworm.com/index.php?rid=5410350&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07508.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5410350 Thu, 17 Nov 2011 04:16:01 +0100 5410350 http://www.medworm.com/index.php?rid=5410349&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07480.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5410349 Thu, 17 Nov 2011 04:15:59 +0100 5410349 http://www.medworm.com/index.php?rid=5410348&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07380.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5410348 Thu, 17 Nov 2011 04:15:58 +0100 5410348 http://www.medworm.com/index.php?rid=5410347&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07557.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5410347 Thu, 17 Nov 2011 04:15:56 +0100 5410347 http://www.medworm.com/index.php?rid=5410346&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07583.x AbstractBrain‐Derived Neurotrophic Factor (BDNF) is required for efficient skeletal‐muscle regeneration and perturbing its expression causes abnormalities in the proliferation and differentiation of skeletal muscle cells. Here, we investigated the mechanism of BDNF suppression that occurs during myogenic differentiation. BDNF is expressed at the mRNA level as two isoforms that differ in the length of their 3’UTRs as a result of alternative cleavage and polyadenylation. Sequence analysis revealed the presence of three miR‐206 target sites in the long BDNF 3’UTR (BDNF‐L), whereas only one site was found in the short mRNA BDNF 3’UTR (BDNF‐S). miR‐206 is known to regulate the differentiation of C2C12 myoblasts and its expression is induced during the transition from myoblasts... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5410346 Thu, 17 Nov 2011 04:14:03 +0100 5410346 http://www.medworm.com/index.php?rid=5477946&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07583.x In this study, we investigated the mechanism of BDNF suppression that occurs during myogenic differentiation. BDNF is expressed at the mRNA level as two isoforms that differ in the length of their 3′UTRs as a result of alternative cleavage and polyadenylation. Sequence analysis revealed the presence of three miR‐206 target sites in the long BDNF 3′UTR (BDNF‐L), whereas only one site was found in the short mRNA BDNF 3′UTR (BDNF‐S). miR‐206 is known to regulate the differentiation of C2C12 myoblasts and its expression is induced during the transition from myoblasts to myotubes. We thus examined whether miR‐206‐mediated suppression is responsible for the expression pattern of BDNF during myogenic differentiation. BDNF‐L was suppressed to a greater extent than BDNF‐S duri... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5477946 Mon, 14 Nov 2011 05:00:00 +0100 5477946 http://www.medworm.com/index.php?rid=5401648&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07580.x AbstractDiscoidin domain receptor 1 (DDR1) is expressed in myelin oligodendrocytes and co‐localizes with myelin basic protein (MBP). Alternative splicing of DDR1 generates five isoforms designated DDR1a‐e. The MBP mRNA contains an A2RE sequence that is recognized by heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, which is responsible for transport of the MBP mRNA to oligodendrocyte processes. We hypothesized that DDR1 could have a functional A2RE sequence. By in silico analysis, we identified an A2RE‐like sequence in the human DDR1 mRNA. We observed nuclear and dendrite cytoplasmic immunofluorescence, indicating that DDR1 and hnRNP A2/B1 co‐localize in human oligodendrocytes and in differentiated HOG16 cells. The A2RE‐like sequence of DDR1 contains the SNP rs2267641, and w... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5401648 Fri, 11 Nov 2011 05:00:00 +0100 5401648 http://www.medworm.com/index.php?rid=5389807&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07568.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5389807 Wed, 09 Nov 2011 05:00:00 +0100 5389807 http://www.medworm.com/index.php?rid=5459480&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07576.x In this study, we report that extracellular application of αSyn oligomers detrimentally impacts neuronal welfare and memory function. We found that oligomeric αSyn increased intracellular Ca2+ levels, induced calcineurin (CaN) activity, decreased cAMP response element‐binding protein (CREB) transcriptional activity and resulted in calcineurin‐dependent death of human neuroblastoma cells. Similarly, CaN induction and CREB inhibition were observed when αSyn oligomers were applied to organotypic brain slices, which opposed hippocampal long‐term potentiation. Furthermore, αSyn oligomers induced CaN, inhibited CREB and evoked memory impairments in mice that received acute intracerebroventricular injections. Notably, all these events were reversed by pharmacological inhibition of CaN. ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459480 Mon, 07 Nov 2011 05:00:00 +0100 5459480 http://www.medworm.com/index.php?rid=5459479&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07578.x This study investigates the role of DMT1, the best‐known iron transporter in mammals, on the mechanisms sustaining non‐transferrin‐bound iron (NTBI) uptake in neurons. The expression analysis of DMT1 isoforms, as well as functional studies of iron uptake, indicate that this transporter does not play a relevant role in neuronal NTBI import. These findings draw the attention to mechanisms other than DMT1‐mediated iron transport in the neuronal iron accumulation observed during aging and in several neurodegenerative disorders. The confocal analysis of the fluorescent DMT1‐1B/IRE(+) overexpressed in hippocampal neurons, reveals a cytoplasmatic punctate staining, similarly to the endogenous protein. The overexpressed DMT1 was recognized by an anti‐DMT1 antibody and showed a colocali... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459479 Mon, 07 Nov 2011 05:00:00 +0100 5459479 http://www.medworm.com/index.php?rid=5389806&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07578.x In this study, we characterize the expression of DMT1 in hippocampal neurons and astrocytes. We found that the main isoform endogenously expressed is DMT1‐1B/IRE(+), which shows cytoplasmic distribution, colocalization with late endosome/lysosome markers and iron regulation, as expected from the presence of an iron responsive element. Our results also show that DMT1‐1B/IRE(+) isoform does not sustain iron entry, even after its neuronal overexpression.Overall, our results argue against a physiological role of the endogenous DMT1 in neuronal iron uptake but do not exclude that, under pathological conditions, the expression of other DMT1 isoforms might contribute to iron overload. (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5389806 Mon, 07 Nov 2011 05:00:00 +0100 5389806 http://www.medworm.com/index.php?rid=5389805&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07577.x AbstractCYP46A1 is a neuron‐specific cytochrome P450 that plays a pivotal role in maintaining cholesterol homeostasis in the CNS. However, the molecular mechanisms underlying human CYP46A1 expression are still poorly understood, partly due to the lack of a cellular model that expresses high levels of CYP46A1. Our previous studies demonstrated that Sp transcription factors control CYP46A1 expression, and are probably responsible for cell‐type specificity. Herein, we have differentiated Ntera2/cloneD1 cells into post‐mitotic neurons and identified for the first time a human cell model that expresses high levels of CYP46A1 mRNA. Our results show a decrease in Sp1 protein levels, concomitant with the increase in CYP46A1 mRNA levels. This decrease was correlated with changes in the ratio ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5389805 Mon, 07 Nov 2011 05:00:00 +0100 5389805 http://www.medworm.com/index.php?rid=5389804&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07576.x AbstractIntracellular deposition of fibrillar aggregates of alpha synuclein (αSyn) characterizes neurodegenerative diseases such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). However, recent evidence indicates that small αSyn oligomeric aggregates that precede fibril formation may be the most neurotoxic species and can be found extracellularly. This new evidence has changed the view of pathological αSyn aggregation from a self‐contained cellular phenomenon to an extracellular event and prompted investigation of the putative effects of extracellular αSyn oligomers. Here, we report that extracellular application of αSyn oligomers detrimentally impacts neuronal welfare and memory function. We found that oligomeric αSyn increased intracellular Ca2+ levels, induced ... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5389804 Mon, 07 Nov 2011 05:00:00 +0100 5389804 http://www.medworm.com/index.php?rid=5365298&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07572.x AbstractLike macrophages, microglia are functionally polarized into different phenotypic activation states, referred as classical and alternative. The balance of the two phenotypes may be critical to ensure proper brain homeostasis, and may be altered in brain pathological states, such as Alzheimer’s disease (AD). We investigated the role of NADPH oxidase in microglial activation state using p47phox and gp91phox deficient mice as well as apocynin, a NADPH oxidase inhibitor during neuroinflammation induced by an intracerebroventricular injection of LPS or Aβ1‐42. We showed that NADPH oxidase plays a critical role in the modulation of microglial phenotype and subsequent inflammatory response. We demonstrated that inhibition of NADPH oxidase or gene deletion of its functional p47phox sub... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5365298 Thu, 03 Nov 2011 04:00:00 +0100 5365298 http://www.medworm.com/index.php?rid=5365297&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07573.x (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5365297 Thu, 03 Nov 2011 04:00:00 +0100 5365297 http://www.medworm.com/index.php?rid=5459481&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07571.x J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07571.xAbstractRecent evidence suggests that the persistence of cocaine seeking during periods of protracted drug abstinence following chronic cocaine exposure is mediated, in part, by neuroadaptations in the mesolimbic dopamine system. Specifically, incubation of cocaine‐seeking behavior coincides with increased brain‐derived neurotrophic factor (BDNF) protein expression in the ventral tegmental area (VTA). However, the molecular mechanisms that regulate time‐dependent changes in VTA BDNF protein expression during cocaine abstinence are unclear. The goal of these experiments was to determine whether VTA BDNF transcript levels are altered following cocaine abstinence and identify the molecular mechanisms regulating cocaine‐induced cha... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5459481 Wed, 02 Nov 2011 04:00:00 +0100 5459481 http://www.medworm.com/index.php?rid=5365300&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07570.x In this study, we investigated the protective roles of lipocalin‐type prostaglandin (PG) D synthase (L‐PGDS) against paraquat‐mediated apoptosis of human neuronal SH‐SY5Y cells. The treatment of SH‐SY5Y cells with paraquat decreased the intracellular GSH level, and enhanced the cell death with elevation of the caspase activities. L‐PGDS was expressed in SH‐SY5Y cells, and its expression was enhanced with the peak at 2 h after the initiation of the treatment with paraquat. Inhibition of PGD2 synthesis and exogenously added PGs showed no effects regarding the paraquat‐mediated apoptosis. SiRNA‐mediated suppression of L‐PGDS expression in the paraquat‐treated cells increased the cell death and caspase activities. Moreover, overexpression of L‐PGDS suppressed the cell d... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5365300 Wed, 02 Nov 2011 04:00:00 +0100 5365300 http://www.medworm.com/index.php?rid=5365299&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07571.x AbstractRecent evidence suggests that the persistence of cocaine seeking during periods of protracted drug abstinence following chronic cocaine exposure is mediated, in part, by neuroadaptations in the mesolimbic dopamine system. Specifically, incubation of cocaine‐seeking behavior coincides with increased brain‐derived neurotrophic factor (BDNF) protein expression in the ventral tegmental area (VTA). However, the molecular mechanisms that regulate time‐dependent changes in VTA BDNF protein expression during cocaine abstinence are unclear. The goal of these experiments was to determine whether VTA BDNF transcript levels are altered following cocaine abstinence and identify the molecular mechanisms regulating cocaine‐induced changes in VTA BDNF transcription. Rats were allowed to se... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5365299 Wed, 02 Nov 2011 04:00:00 +0100 5365299 http://www.medworm.com/index.php?rid=5506702&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07565.x This study analyzes nerve signals and molecular interactions in the PFC to explain how clozapine works. Our findings unify multiple prior hypotheses into one mechanistic model for the action of clozapine. (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5506702 Tue, 01 Nov 2011 04:00:00 +0100 5506702 http://www.medworm.com/index.php?rid=5442953&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07566.x We report that PBEF can ameliorate neuronal death and reduce mitochondrial dysfunction in ischemia. Furthermore, we show the enzymatic activity of PBEF to synthesize NAD+ is required for these beneficial effects. Thus the current study provides insights for potential therapeutic targets for cerebral ischemia. (Source: Journal of Neurochemistry) Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5442953 Tue, 01 Nov 2011 04:00:00 +0100 5442953 http://www.medworm.com/index.php?rid=5401647&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07581.x AbstractMitochondrial dysfunction is a prominent feature of Alzheimer’s disease (AD) brain. Our prior studies demonstrated reduced mitochondrial number in susceptible hippocampal neurons in the brain from AD patients and in M17 cells overexpressing FAD‐causing APP mutant (APPswe). In the current study, we investigated whether alterations in mitochondrial biogenesis contribute to mitochondrial abnormalities in AD. Mitochondrial biogenesis is regulated by the PGC‐1α‐NRF‐TFAM pathway. Expression levels of PGC‐1α, NRF 1, NRF 2, and TFAM were significantly decreased in both AD hippocampal tissues and APPswe M17 cells, suggesting a reduced mitochondrial biogenesis. Indeed, APPswe M17 cells demonstrated decreased mitochondrial DNA/nuclear DNA ratio, correlated with reduced ATP conte... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5401647 Tue, 01 Nov 2011 04:00:00 +0100 5401647 http://www.medworm.com/index.php?rid=5389803&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07579.x We report that blockage of exocytosis in cultured mouse hippocampal neurons, either by tetanus toxin or by the deletion of munc13, inhibits the activity‐dependent redistribution of synapsin from the presynaptic terminal into the axon. Likewise, perturbation of endocytosis with dynasore or by a dynamin dominant‐negative mutant fully prevents synapsin redistribution. Such inhibition of synapsin redistribution occurred despite the efficient phosphorylation of synapsin at its PKA/CaMKI site, indicating that disengagement of synapsin from the vesicles requires exocytosis and endocytosis in addition to phosphorylation. Our results therefore reveal hitherto unidentified feedback within the synaptic vesicle cycle involving the synapsin‐managed reserve pool. (Source: Journal of Neurochemistry... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5389803 Tue, 01 Nov 2011 04:00:00 +0100 5389803 http://www.medworm.com/index.php?rid=5365303&cid=s_32231_25_f&fid=32231&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1471-4159.2011.07566.x AbstractPre‐B‐Cell Colony‐Enhancing Factor (PBEF) is known as a rate‐limiting enzyme that converts nicotinamide (NAM) to NMN in the salvage pathway of mammalian NAD+ biosynthesis. Previously we found PBEF is exclusively expressed in neurons in the mouse brain; heterozygous PBEF knockout (Pbef+/‐) mice have larger ischemic lesion than wild type mice in photothrombosis‐induced ischemia. For the mechanistic study of neuronal protective role of PBEF, we used in vitro oxygen‐glucose deprivation (OGD) and glutamate excitotoxicity models of primary cultured neurons in current study. Our results showed that the treatments of neurons with NAM and NAD+, the substrate and downstream product of PBEF, respectively, significantly reduced neuronal death after OGD and glutamate excitotoxicit... Journal of Neurochemistry journals http://www.medworm.com/rss/comments.php?id=5365303 Tue, 01 Nov 2011 04:00:00 +0100 5365303