Journal of NeuroImmune Pharmacology
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Manipulating Antigenic Ligand Strength to Selectively Target Myelin-Reactive CD4+ T Cells in EAE
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Abstract The development of antigen-specific therapies for the selective tolerization of autoreactive T cells remains the Holy Grail
for the treatment of T-cell-mediated autoimmune diseases such as multiple sclerosis (MS) and its animal model experimental
autoimmune encephalomyelitis (EAE). This quest remains elusive, however, as the numerous antigen-specific strategies targeting
myelin-specific T cells over the years have failed to result in clinical success. In this review, we revisit the antigen-based
therapies used in the treatment of myelin-specific CD4+ T cells in the context of the functional avidity ...
Source: Journal of NeuroImmune Pharmacology - November 11, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Lipopolysaccharide Increases the Expression of Multidrug Resistance-Associated Protein 1 (MRP1) in RAW 264.7 MacrophagesEmail this article to a colleague.
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Abstract Multidrug resistance-associated protein 1 (MRP-1) is a ubiquitously expressed member of the ATP-binding cassette transporter
family. MRP-1 is one of the primary transporters of glutathione and glutathione conjugates. This protein also transports antiretroviral
therapeutics, such as HIV-1 protease inhibitors (PI). We hypothesized that inflammatory mediators that activate macrophages
would modify the expression and activity of MRP-1 in macrophages. Real-time PCR assays, western blots, and calcein efflux
assays were used to show that exposure of macrophage cell line RAW 264.7 to lipopolysaccharide (LPS...
Source: Journal of NeuroImmune Pharmacology - November 5, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Neuropathogenesis of Theiler’s Murine Encephalomyelitis Virus Infection, An Animal Model for Multiple SclerosisEmail this article to a colleague.
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Abstract Theiler’s murine encephalomyelitis virus (TMEV) infection of mice is an experimental model for multiple sclerosis (MS). TMEV
induces a biphasic disease in susceptible mouse strains. During the acute phase, 1 week after infection, TMEV causes polioencephalomyelitis
characterized by infection and apoptosis of neurons in the gray matter of the brain. During the chronic phase, about 1 month
after infection, virus infects glial cells and macrophages, and induces inflammatory demyelination with oligodendrocyte apoptosis
and axonal degeneration in the white matter of the spinal cord. Although a...
Source: Journal of NeuroImmune Pharmacology - November 5, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Non-CB1, Non-CB2 Receptors for Endocannabinoids, Plant Cannabinoids, and Synthetic Cannabimimetics: Focus on G-protein-coupled Receptors and Transient Receptor Potential ChannelsEmail this article to a colleague.
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Abstract The molecular mechanism of action of Δ9-tetrahydrocannabinol (THC), the psychotropic constituent of Cannabis, has been a puzzle during the three decades separating its characterization, in 1964, and the cloning, in the 1990s, of cannabinoid
CB1 and CB2 receptors. However, while these latter proteins do mediate most of the pharmacological actions of THC, they do not seem to
act as receptors for other plant cannabinoids (phytocannabinoids), nor are they the unique targets of the endogenous lipids
that were originally identified in animals as agonists of CB1 and CB2 receptors, and named endocannabinoid...
Source: Journal of NeuroImmune Pharmacology - October 21, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Experimental Autoimmune Encephalomyelitis in the Common Marmoset, a Bridge Between Rodent EAE and Multiple Sclerosis for Immunotherapy DevelopmentEmail this article to a colleague.
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Abstract The attrition rate of new drugs for central nervous system diseases including multiple sclerosis (MS) is very high. A widely
recognized bottleneck in the selection of promising central nervous system drug candidates from the development pipeline is
the lack of sufficiently predictive animal models. Here, we review how the experimental autoimmune encephalomyelitis (EAE)
model in the Neotropical primate “common marmoset” can help to bridge the gap between rodent EAE models and MS. The EAE model
in the marmoset closely resembles MS in the clinical as well as pathological presentation and can be use...
Source: Journal of NeuroImmune Pharmacology - October 13, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Neuroinflammation in Parkinson’s DiseaseEmail this article to a colleague.
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Abstract During the last two decades, a wealth of animal and human studies has implicated inflammation-derived oxidative stress and
cytokine-dependent neurotoxicity in the progressive degeneration of the dopaminergic nigrostriatal pathway, the hallmark of
Parkinson’s disease (PD). In this review, we discuss the various hypotheses regarding the role of microglia and other immune
cells in PD pathogenesis and progression, the inflammatory mechanisms implicated in disease progression from pre-clinical
and clinical studies, the recent evidence that systemic inflammation can trigger microglia activation in PD-re...
Source: Journal of NeuroImmune Pharmacology - October 10, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Recombinant TCR Ligand Reverses Clinical Signs and CNS Damage of EAE Induced by Recombinant Human MOGEmail this article to a colleague.
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We report that RTL551 therapy can reverse disease progression and reduce demyelination and axonal damage induced by
rhMOG without suppressing the anti-MOG antibody response. This result suggests that T cell-mediated inflammation and associated
blood–brain barrier dysfunction are the central contributors to EAE pathogenesis and that successful regulation of these key
players restricts potential damage by demyelinating antibodies. The results of our study lend support for the use of RTL therapy
for treatment of MS subjects whose disease includes inflammatory T cells as well as those with an additional antibody componen...
Source: Journal of NeuroImmune Pharmacology - September 29, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
CNS Inflammation and Macrophage/Microglial Biology Associated with HIV-1 InfectionEmail this article to a colleague.
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Abstract Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) can result in neurological dysfunction
with devastating consequences in a significant proportion of individuals with acquired immune deficiency syndrome. HIV-1 does
not infect neurons directly but induces damage indirectly through the accumulation of activated macrophage/microglia (M/M)
cells, some of which are infected, that release neurotoxic mediators including both cellular activation products and viral
proteins. One mechanism for the accumulation of activated M/M involves the development in infected indivi...
Source: Journal of NeuroImmune Pharmacology - September 18, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Microglia in Central Nervous System DiseasesEmail this article to a colleague.
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Content Type Journal ArticleCategory Guest CommentaryDOI 10.1007/s11481-009-9173-3Authors
Gary E. Landreth, Case Western Reserve University School of Medicine Alzheimer Research Laboratory, Department of Neurosciences 10900 Euclid Ave. Cleveland OH 44106 USA
Journal Journal of Neuroimmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - September 18, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Identification of Transcription Start Sites and Preferential Expression of Select CB2 Transcripts in Mouse and Human B LymphocytesEmail this article to a colleague.
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Abstract Marijuana cannabinoids, the endocannabinoids, and cannabinoid cell receptors have been shown to play important roles in immune
regulation particularly as potent modulators of anti-inflammatory cytokines. The predominant cannabinoid receptor involved
in this immune regulation is cannabinoid receptor 2 (CB2), which is predominantly expressed in B lymphocytes. However, the promoter region and mechanisms of CB2 gene regulation are unknown in this immune cell type. Utilizing a combination of bioinformatics, 5′ rapid amplification of
cDNA ends (5′ RACE), real-time reverse transcription-polymerase chain...
Source: Journal of NeuroImmune Pharmacology - September 15, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Defining Larger Roles for “Tiny” RNA Molecules: Role of miRNAs in Neurodegeneration ResearchEmail this article to a colleague.
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Abstract Many facets of transcriptional and translational regulation contribute to the proper functioning of the nervous system. Dysfunctional
control of mRNA and protein expression can lead to neurodegenerative conditions. Recently, a new regulatory control element—small
noncoding RNAs—has been found to play a significant role in many physiologic systems. Here, we review the microRNA (miRNA)
field as it pertains to discovery-based and mechanistic studies on the brain and specifically in neurodegenerative disorders.
Understanding the role of miRNAs in the brain will aid to open new avenues to the field o...
Source: Journal of NeuroImmune Pharmacology - September 15, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Microglia in ALS: The Good, The Bad, and The RestingEmail this article to a colleague.
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Abstract Inflammation, including microglial activation and T cell infiltration, is a neuropathological hallmark of amyotrophic lateral
sclerosis (ALS), a rapidly progressing neurodegenerative disease. The identification of mutations in the gene for Cu2+/Zn2+ superoxide dismutase (SOD1) from patients with an inherited form of ALS enabled the creation of transgenic mice overexpressing
mutant forms of SOD1 (mSOD1) which develop a motoneuron disease that resembles the disease seen in ALS patients. These transgenic
mice display similar inflammatory reactions at sites of motoneuron injury as detected in ALS patient...
Source: Journal of NeuroImmune Pharmacology - September 15, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Microglia in Infectious Diseases of the Central Nervous SystemEmail this article to a colleague.
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Abstract Microglia are the resident macrophage population in the central nervous system (CNS) parenchyma and, as such, are poised to
provide a first line of defense against invading pathogens. Microglia are endowed with a vast repertoire of pattern recognition
receptors that include such family members as Toll-like receptors and phagocytic receptors, which collectively function to
sense and eliminate microbes invading the CNS parenchyma. In addition, microglial activation elicits a broad range of pro-inflammatory
cytokines and chemokines that are involved in the recruitment and subsequent activation of perip...
Source: Journal of NeuroImmune Pharmacology - September 3, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Gene Expression Profiles of HIV-1-Infected Glia and Brain: Toward Better Understanding of the Role of Astrocytes in HIV-1-Associated Neurocognitive DisordersEmail this article to a colleague.
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Abstract Astrocytes are the major cellular component of the central nervous system (CNS), and they play multiple roles in brain development,
normal brain function, and CNS responses to pathogens and injury. The functional versatility of astrocytes is linked to their
ability to respond to a wide array of biological stimuli through finely orchestrated changes in cellular gene expression.
Dysregulation of gene expression programs, generally by chronic exposure to pathogenic stimuli, may lead to dysfunction of
astrocytes and contribute to neuropathogenesis. Here, we review studies that employ functional genomics...
Source: Journal of NeuroImmune Pharmacology - August 21, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Synaptic Proteins Linked to HIV-1 Infection and Immunoproteasome Induction: Proteomic Analysis of Human SynaptosomesEmail this article to a colleague.
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Abstract Infection of the central nervous system with human immunodeficiency virus type 1 (HIV-1) can produce morphological changes
in the neocortical synaptodendritic arbor that are correlated with neurocognitive impairment. To determine whether HIV-1 infection
influences the protein composition of human synapses, a proteomic study of isolated nerve endings was undertaken. Synaptosomes
from frontal neocortex were isolated using isopyknic centrifugation from 19 human brain specimens. Purity and enrichment were
assessed by measuring pre- and postsynaptic protein markers. Two-dimensional polyacrylamide gel ele...
Source: Journal of NeuroImmune Pharmacology - August 19, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Life and Death of MicrogliaEmail this article to a colleague.
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Abstract The importance of microglial cells in the maintenance of a well-functioning central nervous system (CNS) cannot be overstated.
As descendants of the myelomonocytic lineage they are industrious housekeepers and watchful sentries that safeguard a homeostatic
environment through a number of mechanisms designed to provide protection of fastidious neurons at all times. Microglia become
particularly active after homeostasis has been perturbed by physical injury or other insults and they enter into a state of
activation which is determined largely by the nature and severity of the lesion. Microglial activa...
Source: Journal of NeuroImmune Pharmacology - August 14, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
CNS Infiltration of Peripheral Immune Cells: D-Day for Neurodegenerative Disease?Email this article to a colleague.
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Abstract While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known
as “immune privilege,” it is now clear that immune responses do occur in the CNS—giving rise to the field of neuroimmunology.
These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve
either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral
monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West...
Source: Journal of NeuroImmune Pharmacology - August 11, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Inflammation and Microglia Actions in Alzheimer’s DiseaseEmail this article to a colleague.
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Abstract A variety of studies have documented increased presence of reactive microglia in the brains of not only Alzheimer’s disease
(AD) patients but its transgenic mouse models. Since these cells are often characterized in association with fibrillar Aβ
peptide-containing plaques, it has been assumed that plaque interaction provides one stimulus for the phenotype observed.
The growing appreciation that microglia phenotype changes with age and that resident immune cells are comingled with blood-derived
macrophage has complicated understanding of the behavior of these cells in AD. In addition, comparison o...
Source: Journal of NeuroImmune Pharmacology - August 11, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Heterogeneity of Microglial Activation in the Innate Immune Response in the BrainEmail this article to a colleague.
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Abstract The immune response in the brain has been widely investigated and while many studies have focused on the proinflammatory cytotoxic
response, the brain’s innate immune system demonstrates significant heterogeneity. Microglia, like other tissue macrophages,
participate in repair and resolution processes after infection or injury to restore normal tissue homeostasis. This review
examines the mechanisms that lead to reduction of self-toxicity and to repair and restructuring of the damaged extracellular
matrix in the brain. Part of the resolution process involves switching macrophage functional activat...
Source: Journal of NeuroImmune Pharmacology - August 4, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Imaging Mass Spectrometry for Visualization of Drug and Endogenous Metabolite Distribution: Toward In Situ PharmacometabolomesEmail this article to a colleague.
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Abstract It is important to determine how a candidate drug is distributed and metabolized within the body in early phase of drug discovery.
Recently, matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS; also referred to as mass spectrometry
imaging) has attracted great interest for monitoring drug delivery and metabolism. Since this emerging technique enables simultaneous
imaging of many types of metabolite molecules, MALDI-IMS can visualize and distinguish the parent drug and its metabolites.
As another important advantage, changes in endogenous metabolites in response to drug...
Source: Journal of NeuroImmune Pharmacology - June 10, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
4-Aminopyridine Improves Spatial Memory in a Murine Model of HIV-1 EncephalitisEmail this article to a colleague.
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Abstract HIV-1-associated neurocognitive disorders (HAND) remains a significant source of morbidity in the era of wide spread use of
highly active antiretroviral therapy. Disease is precipitated by low levels of viral growth and glial immune activation within
the central nervous system. Blood borne macrophage and microglia affect a proinflammatory response and release viral proteins
that affects neuronal viability and leads to death of nerve cells. Increasing evidence supports the notion that HAND is functional
channelopathy, but proof of this concept remains incomplete. Based on their role in learning and m...
Source: Journal of NeuroImmune Pharmacology - May 22, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Planning Future Strategies for Domestic and International NeuroAIDS Research, July 24–25, 2008Email this article to a colleague.
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Abstract The National Institute of Mental Health in cooperation with the National Institute on Drug Abuse and the National Institute
of Neurological Disorders and Stroke organized a meeting on July 24–25, 2008 to develop novel research directions for neuroAIDS
research. The deliberations of this meeting are outlined in this brief report. Several critical research areas in neuroAIDS
were identified as areas of emphasis. Opportunities for collaborations between large NIH-funded projects were also discussed.
Content Type Journal ArticleCategory Brief ReportDOI 10.1007/s11481-009-9159-1Authors
Jeymohan Jos...
Source: Journal of NeuroImmune Pharmacology - May 20, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Methamphetamine-Induced Behavioral Sensitization Is Enhanced in the HIV-1 Transgenic RatEmail this article to a colleague.
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Abstract Methamphetamine (METH) addiction is prevalent among individuals with HIV infection. We hypothesize that HIV-positive individuals
are more prone to METH use and to the development of METH dependence. To test this hypothesis, we examined the effects of
METH (daily intraperitoneal injection 2.5 mg/kg for 6 days) on rearing and head movement in 12–13-week-old male HIV-1 transgenic
(HIV-1Tg) rats compared to F344 control rats as an indicator of behavioral sensitization, also representing neural adaptation
underlying drug dependence and addiction. Body and brain weights were also recorded. The...
Source: Journal of NeuroImmune Pharmacology - May 15, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Curcumin Protects Neuronal Cells from Japanese Encephalitis Virus-Mediated Cell Death and also Inhibits Infective Viral Particle Formation by Dysregulation of Ubiquitin–Proteasome SystemEmail this article to a colleague.
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In this study, we found
that curcumin imparts neuroprotection in vitro, probably by decreasing cellular reactive oxygen species level, restoration
of cellular membrane integrity, decreasing pro-apoptotic signaling molecules, and modulating cellular levels of stress-related
proteins. We have also shown that curcumin, by inhibition of ubiquitin–proteasome system causes reduction in infective viral
particle production from previously infected neuroblastoma cells.
Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s11481-009-9158-2Authors
Kallol Dutta, National Brain Research Centre Manesar Haryana 122...
Source: Journal of NeuroImmune Pharmacology - May 12, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Database Resources in Metabolomics: An OverviewEmail this article to a colleague.
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Abstract Metabolomics is the characterization, identification, and quantitation of metabolites resulting from a wide range of biochemical
processes in living systems. Its rapid development over the past few years has increased the demands for bioinformatics and
cheminformatics resources that span from data processing tools, comprehensive databases, statistical tools, and computational
tools for modeling metabolic networks. With the wealth of information that is being amassed, new types of metabolomic databases
are emerging that are not only designed to store, manage, and analyze metabolomic data but are also...
Source: Journal of NeuroImmune Pharmacology - May 6, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
The Aging of Human-Immunodeficiency-Virus-Associated Neurocognitive DisordersEmail this article to a colleague.
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Content Type Journal ArticleCategory Guest CommentaryDOI 10.1007/s11481-009-9155-5Authors
Tsuneya Ikezu, University of Nebraska Medical Center Department of Pharmacology and Experimental Neuroscience, Center for Neurodegenerative Disorders 985880 Nebraska Medical Center Omaha NE 68198-5880 USA
Journal Journal of Neuroimmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - May 5, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Metabolomics: Moving to the ClinicEmail this article to a colleague.
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Abstract Assessment of a biological system by means of global and non-targeted metabolite profiling—metabolomics or metabonomics—provides
the investigator with molecular information that is close to the phenotype in question in the sense that metabolites are an
ultimate product of gene, mRNA, and protein activity. Over the last few years, there has been a rapidly growing number of
metabolomics applications aimed at finding biomarkers which could assist diagnosis, provide therapy guidance, and evaluate
response to therapy for particular diseases. Also, within the fields of drug discovery, drug toxicology,...
Source: Journal of NeuroImmune Pharmacology - April 28, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Host and Viral Factors Influencing the Pathogenesis of HIV-Associated Neurocognitive DisordersEmail this article to a colleague.
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Abstract The human immunodeficiency virus (HIV) invades the central nervous system early in the course of infection and establishes
a protected viral reservoir. However, neurocognitive consequences of HIV infection, known collectively as HIV-associated neurocognitive
disorders (HAND), develop in only a small portion of infected patients. The precise mechanisms of pathogenesis involved in
HIV-induced central nervous system injury are still not completely understood. In particular, most theories of HAND pathogenesis
cannot account for either the selective vulnerability of specific neuronal populations to HIV-i...
Source: Journal of NeuroImmune Pharmacology - April 17, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Cannabinoid Regulation of Nitric Oxide Synthase I (nNOS) in Neuronal CellsEmail this article to a colleague.
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Abstract In our previous studies, CB1 cannabinoid receptor agonists stimulated production of cyclic GMP and translocation of nitric oxide (NO)-sensitive guanylyl
cyclase in neuronal cells (Jones et al., Neuropharmacology 54:23–30, 2008). The purpose of these studies was to elucidate the signal transduction of cannabinoid-mediated neuronal nitric oxide synthase
(nNOS) activation in neuronal cells. Cannabinoid agonists CP55940 (2-[(1S,2R,5S)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-5-(2-methyloctan-2-yl)phenol), WIN55212-2 (R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-...
Source: Journal of NeuroImmune Pharmacology - April 14, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Tumor Necrosis Factor-alpha Levels in HIV-1 Seropositive Injecting Drug UsersEmail this article to a colleague.
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Abstract TNF-α is a highly pleiotropic cytokine and plays an important role in regulating HIV-1 replication. It may compromise the
integrity of the blood-brain-barrier and, thus, may contribute to the neurotoxicity of HIV-1-infection. Both intravenous drug
abuse (IDU) and HIV infection can increase TNF-α activity, but little information is available on the effects of a combination
of these factors on TNF-α. We investigated plasma TNF-α levels and mRNA in the peripheral monocytes of 166 men and women in
three groups: HIV-1-positive IDUs, HIV-1-negative IDUs, and HIV-negative non-IDU control participants. ...
Source: Journal of NeuroImmune Pharmacology - April 5, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Increased Accumulation of Intraneuronal Amyloid β in HIV-Infected PatientsEmail this article to a colleague.
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Abstract In recent years, human immunodeficiency virus (HIV)-infected patients under highly active anti-retroviral therapy (HAART)
regimens have shown a markedly improved general clinical status; however, the prevalence of mild cognitive disorders has increased.
We propose that increased longevity with HIV-mediated chronic inflammation combined with the secondary effects of HAART may
increase the risk of early brain aging as shown by intraneuronal accumulation of abnormal protein aggregates like amyloid
β (Aβ), which might participate in worsening the neurodegenerative process and cognitive impairment in o...
Source: Journal of NeuroImmune Pharmacology - March 16, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
HIV Regulation of Amyloid Beta ProductionEmail this article to a colleague.
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Abstract The use of antiretroviral therapy for HIV infection has extended the survival of individuals living with HIV. However, the
effects of chronic HIV infection and aging are introducing another facet of HIV complications. HIV therapy can calm the immune
system and lower viral replication to undetectable but the virus is still present. In the brain, amyloid beta (Aβ) increases
during normal aging but Aβ accumulation appears to accelerate in HIV infection. HIV Tat protein inhibits the major Aβ-degrading
enzyme neprilysin with the cysteine-rich domain of Tat being essential for this inhibition. In this ...
Source: Journal of NeuroImmune Pharmacology - March 14, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Rhesus Macaque Model of Chronic Opiate Dependence and Neuro-AIDS: Longitudinal Assessment of Auditory Brainstem Responses and Visual Evoked PotentialsEmail this article to a colleague.
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Abstract Our work characterizes the effects of opiate (morphine) dependence on auditory brainstem and visual evoked responses in a
rhesus macaque model of neuro-AIDS utilizing a chronic continuous drug delivery paradigm. The goal of this study was to clarify
whether morphine is protective, or if it exacerbates simian immunodeficiency virus (SIV)-related systemic and neurological
disease. Our model employs a macrophage tropic CD4/CCR5 coreceptor virus, SIVmac239 (R71/E17), which crosses the blood-brain barrier shortly after inoculation and closely mimics the natural disease course
of human immunodeficiency vi...
Source: Journal of NeuroImmune Pharmacology - March 13, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Modulation of Cannabinoid Receptor Activation as a Neuroprotective Strategy for EAE and StrokeEmail this article to a colleague.
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In this report,
we present evidence that activation of CB2 receptors, by selective CB2 agonists, reduces inflammatory responses that contribute to CNS injury. The studies demonstrate neuroprotective effects in
experimental autoimmune encephalomyelitis, a model of multiple sclerosis, and in a murine model of cerebral ischemia/reperfusion
injury. In both cases, CB2 receptor activation results in reduced white cell rolling and adhesion to cerebral microvessels, a reduction in immune cell
invasion, and improved neurologic function after insult. In addition, administration of the CB1 antagonist SR141716A reduces infarct siz...
Source: Journal of NeuroImmune Pharmacology - March 3, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
WIN55,212-2 Inhibits Production of CX3CL1 by Human Astrocytes: Involvement of p38 MAP KinaseEmail this article to a colleague.
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In this study, we found that production of CX3CL1 by human astrocytes stimulated with interleukin (IL)-1β was inhibited in
a concentration-dependent manner following pretreatment with the synthetic cannabinoid WIN55,212-2. The CB2 receptor selective antagonist SR144528 significantly inhibited WIN55,212-2-mediated suppression of CX3CL1, suggesting a CB2-receptor-related mechanism. IL-1β triggered the activation of p38 and ERK1/2 (p44/42) MAP kinase (MAPK) signaling pathways,
but WIN55,212-2 mainly inhibited p38 MAPK phosphorylation. This finding was mirrored in experiments using known inhibitors
of these MAPKs, suggest...
Source: Journal of NeuroImmune Pharmacology - February 13, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Differential Expression of Immunophilins FKBP51 and FKBP52 in the Frontal Cortex of HIV-Infected Patients with Major Depressive DisorderEmail this article to a colleague.
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Abstract Patients infected with human immunodeficiency virus (HIV) have a higher risk of developing major depressive disorder (MDD)
than the general population. Immunophilins FKBP51 and FKBP52 are expressed in cortical neurons and regulate the function of
the glucocorticoid receptor (GR). Previous reports have shown that genetic variants in the FKBP5 gene encoding FKBP51 are linked to psychiatric disorders. We sought to determine whether immunophilins are upregulated in
HIV infection. To determine whether FKBP52 and FKBP51 are associated with MDD and/or HIV, we compared protein and gene expression
in autopsy...
Source: Journal of NeuroImmune Pharmacology - February 7, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Inducible Expression of Functional Mu Opioid Receptors in Murine Dendritic CellsEmail this article to a colleague.
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Abstract Opioids are known to exert direct effects on the immune system, and the expression of functional opioid receptors has been
reported on several immune cell types. Dendritic cells (DCs) are important inducers and regulators of immune responses. In
this study, we investigated whether murine dendritic cells express functional mu opioid receptors (MOR). RT-PCR analysis and
double immunofluorescence staining revealed the expression of MOR in activated murine dendritic cells. We also studied the
dynamic expression of MOR messenger RNA in murine dendritic cells in response to different Toll-like receptor li...
Source: Journal of NeuroImmune Pharmacology - February 3, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Nanobiology for the Pharmacology of Cellular Ion ChannelsEmail this article to a colleague.
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Abstract Writing this editorial is especially pleasing. First, it provides us an opportunity to introduce new directives to the field of Neuroimmune Pharmacology and to explain why the
field of nanomedicine is likely an important part of its future growth and development. Second, it is an opportunity to showcase research in this area currently operative in Russia that may not be readily accessible
to the readership. Third, it is a platform to better explain why the Journal Editorial leadership was enthusiastic about the science and its relationship
to the Society on NeuroImmune Pharmacology strategic goals. A...
Source: Journal of NeuroImmune Pharmacology - January 24, 2009 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Neurodegeneration and Ageing in the HAART EraEmail this article to a colleague.
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Abstract Cognitive impairment and neurodegeneration still occur despite highly active antiretroviral therapy (HAART). While there are
many potential reasons for this, there is increasing evidence that such impairment occurs in the absence of a clear cause.
Furthermore, there are data that some neurodegenerative diseases, especially Alzheimer’s or an Alzheimer-like illness, are
becoming more common in the context of HAART-treated human immunodeficiency virus (HIV) disease. This review will critically
examine the evidence underpinning these observations. Potential mechanisms will be discussed with particular...
Source: Journal of NeuroImmune Pharmacology - December 10, 2008 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Imaging Microglial Activation During Neuroinflammation and Alzheimer’s DiseaseEmail this article to a colleague.
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Abstract Microglial activation is an important pathogenic component of neurodegenerative disease processes. This state of increased
inflammation is associated not only with neurotoxic consequences but also neuroprotective effects, e.g., phagocytosis and
clearance of amyloid in Alzheimer’s disease. In addition, activation of microglia appears to be one of the major mechanisms
of amyloid clearance following active or passive immunotherapy. Imaging techniques may provide a minimally invasive tool to
elucidate the complexities and dynamics of microglial function and dysfunction in aging and neurodegenerative d...
Source: Journal of NeuroImmune Pharmacology - December 4, 2008 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Lipopolysaccharide Impairs Blood–Brain Barrier P-glycoprotein Function in Mice Through Prostaglandin- and Nitric Oxide-Independent PathwaysEmail this article to a colleague.
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Abstract P-glycoprotein (P-gp) is a brain-to-blood efflux system that controls the ability of many drugs and endogenous substances
to access the brain. In vitro work has shown that inflammatory states mediated through lipopolysaccharide (LPS) and tumor
necrosis factor-alpha first impair and then stimulate P-gp activity. Here, we determined whether LPS can affect P-gp function
in vivo. Mice treated with a single intraperitoneal injection of LPS (3 mg/kg) showed an inhibition of P-gp function. As assessed
by brain perfusion, inhibition began 18 h after LPS administration and lasted until 36 h af...
Source: Journal of NeuroImmune Pharmacology - November 28, 2008 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Monocyte Chemotactic Protein-1 Regulates Voltage-Gated K+ Channels and Macrophage TransmigrationEmail this article to a colleague.
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Abstract Progressive human immunodeficiency virus (HIV)-1 infection and virus-induced neuroinflammatory responses effectuate monocyte-macrophage
transmigration across the blood–brain barrier (BBB). A key factor in mediating these events is monocyte chemotactic protein-1
(MCP-1). Upregulated glial-derived MCP-1 in HIV-1-infected brain tissues generates a gradient for monocyte recruitment into
the nervous system. We posit that the inter-relationships between MCP-1, voltage-gated ion channels, cell shape and volume,
and cell mobility underlie monocyte transmigration across the BBB. In this regard, MCP-1 serve...
Source: Journal of NeuroImmune Pharmacology - November 26, 2008 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Calpain and Proteasomal Regulation of Antiretroviral Zinc Finger Protein OTK18 in Human Macrophages: Visualization in Live Cells by Intramolecular FRETEmail this article to a colleague.
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Abstract As part of the innate immune defense against HIV infection, OTK18, a zinc finger protein, is upregulated in human macrophages
and reduces viral replication through suppression of viral long-terminal repeat promoter activity. Although we know that the
processing products of OTK18 accumulate in the cytoplasm of brain perivascular macrophages in advanced HIV encephalitis cases,
the molecular mechanisms behind its post-translational processing are still poorly understood. To characterize OTK18 processing,
we assessed a panel of protease inhibitors to identify the candidates involved in the OTK18 process...
Source: Journal of NeuroImmune Pharmacology - November 26, 2008 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
YY1 and FoxD3 Regulate Antiretroviral Zinc Finger Protein OTK18 Promoter Activation Induced by HIV-1 InfectionEmail this article to a colleague.
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Abstract OTK18 is a C2H2 type zinc finger protein involved in the regulation of HIV-1 replication in human mononuclear phagocytes. Previously, we
reported OTK18 expression in brain perivascular macrophages but not in microglia in HIV encephalitis brain. We have cloned
the OTK18 promoter region proximal to the transcriptional start site and determined the region responsible (−884/+1) for the
basal transcriptional activity in a microglia cell line. Sequential deletion mutation analyses reveal three important response
elements: Yingyang-1 (YY1; −805/−777), an HIV-1 response element for promoter activation...
Source: Journal of NeuroImmune Pharmacology - November 26, 2008 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
M- and T-tropic HIVs Promote Apoptosis in Rat NeuronsEmail this article to a colleague.
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Abstract Neuronal loss, reactive astrocytes, and other abnormalities are seen in the brain of individuals with acquired immune deficiency
syndrome-associated Dementia Complex (ADC). Human immunodeficiency virus-1 (HIV-1) is believed to be the main agent causing
ADC. However, little is known about the molecular and cellular mechanisms of HIV-1 neurotoxicity considering that HIV-1 does
not infect post-mitotic neurons and that viral load does not necessarily correlate with ADC. Various viral proteins, such
as the envelope protein gp120 and the transcription activator Tat, have been shown to induce neuronal apop...
Source: Journal of NeuroImmune Pharmacology - November 26, 2008 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
TNF Alpha Production in Morphine-Treated Human Neural Cells Is NF-κB-DependentEmail this article to a colleague.
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This study examines the role of NF-κB in the regulation of TNFα
production by morphine in microglia. Using reverse transcriptase polymerase chain reaction, we demonstrated the presence of
morphine receptors in these cells. We next demonstrated the ability of morphine to promote TNFα production and secretion by
these cells using a cytokine array assay. Transient transfection experiments led to the identification of the region located
between nucleotides −751 and −615 within the TNFα promoter as being responsive to morphine treatment. The DNA sequence of
this region contains a motif indicative of a potential NF-...
Source: Journal of NeuroImmune Pharmacology - November 21, 2008 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
The Comorbidity of HIV-Associated Neurocognitive Disorders and Alzheimer’s Disease: A Foreseeable Medical Challenge in Post-HAART EraEmail this article to a colleague.
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Abstract Although the introduction of highly active antiretroviral therapy (HAART) has led to a strong reduction of HIV-associated
dementia (HAD) incidence, the prevalence of minor HIV-1-associated neurocognitive disorder (HAND) is rising among AIDS patients.
HAART medication has shifted neuropathology from a subacute encephalitic condition to a subtle neurodegenerative process involving
synaptic and dendritic degeneration, particularly of hippocampal neurons that are spared prior to HAART medication. Considerable
neuroinflammation coupled with mononuclear phagocyte activation is present in HAART-medicated b...
Source: Journal of NeuroImmune Pharmacology - November 19, 2008 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
SNIP Members in a Recent International Conference: World Summit of AntiviralsEmail this article to a colleague.
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Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s11481-008-9134-2Authors
Huangui Xiong, University of Nebraska Medical Center Department of Pharmacology and Experimental Neuroscience 985880 Nebraska Medical Center Omaha NE 68198-5880 USASulie L. Chang, Seton Hall University Institute of Neuroimmune Pharmacology, The College of Arts and Science South Orange NJ 07079 USAShilpa Buch, University of Kansas Medical Center Department of Molecular and Integrative Physiology Kansas City KS 66160 USASabita Roy, University of Minnesota Division of Infection, Inflammation and Vascular Biology, Department of Su...
Source: Journal of NeuroImmune Pharmacology - November 11, 2008 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
Methamphetamine Enhances HIV-1 Infectivity in Monocyte Derived Dendritic CellsEmail this article to a colleague.
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We report that Meth enhances HIV-1 infectivity of dendritic cells as
measured by multinuclear activation of a galactosidase indicator (MAGI) cell assay, p24 assay, and LTR-RU5 amplification.
Meth induces increased HIV-1 infection in association with an increase in the HIV-1 coreceptors, CXCR4 and CCR5, and infection
is mediated by downregulation of extracellular-regulated kinase (ERK2) and the upregulation of p38 mitogen-activated protein
kinase (MAPK). A p38 inhibitor (SB203580) specifically reversed the Meth-induced upregulation of the CCR5 HIV-1 coreceptor.
The dopamine D2 receptor antagonist RS ± sulpir...
Source: Journal of NeuroImmune Pharmacology - October 29, 2008 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
The Promise and Perils of an Alzheimer Disease Vaccine: A Video DebateEmail this article to a colleague.
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Abstract Alzheimer’s disease (AD) is a critical health care problem that has considerable social and economic impact on society. Effective
treatments have been elusive. One major causal factor for the disease is believed to be the deposition of amyloid fibrils
in the brain, which ultimately leads to neurodegeneration and cognitive dysfunction. Based on the amyloid hypothesis of Alzheimer’s
disease, many therapies presently target the amyloid beta (Aβ) peptide, the monomeric protein fragment that assembles to form
fibrils. This video article takes the form of a debate between Dr. Morgan and Dr. Landreth ...
Source: Journal of NeuroImmune Pharmacology - October 23, 2008 Category: Drugs & Pharmacology Tags: Journal of Neuroimmune Pharmacology Source Type: journals
