Cocaine Induces Nuclear Export and Degradation of Neuronal Retinoid X Receptor-γ via a TNF-α/JNK- Mediated Mechanism
Abstract Cocaine abuse represents an immense societal health and economic burden for which no effective treatment currently exists. Among the numerous intracellular signaling cascades impacted by exposure to cocaine, increased and aberrant production of pro-inflammatory cytokines in the CNS has been observed. Additionally, we have previously reported a decrease in retinoid-X-receptor-gamma (RXR-γ) in brains of mice chronically exposed to cocaine. Through obligate heterodimerization with a number of nuclear receptors, RXRs serve as master regulatory transcription factors, which can potentiate or suppress expr...
Source: Journal of NeuroImmune Pharmacology - January 14, 2015 Category: Drugs & Pharmacology Source Type: research

Metabolomic Approaches to Defining the Role(s) of GABA ρ Receptors in the Brain
Abstract The inhibitory neurotransmitter γ-aminobutyric acid (GABA) acts through various types of receptors in the central nervous system. GABAρ receptors, defined by their characteristic pharmacology and presence of ρ subunits in the channel structure, are poorly understood and their role in the cortex is ill-defined. Here, we used a targeted pharmacological, NMR-based functional metabolomic approach in Guinea pig brain cortical tissue slices to identify a distinct role for these receptors. We compared metabolic fingerprints generated by a range of ligands active at GABAρ and included these in a...
Source: Journal of NeuroImmune Pharmacology - January 11, 2015 Category: Drugs & Pharmacology Source Type: research

Independent and Co-morbid HIV Infection and Meth Use Disorders on Oxidative Stress Markers in the Cerebrospinal Fluid and Depressive Symptoms
Abstract Both HIV infection and Methamphetamine (Meth) use disorders are associated with greater depressive symptoms and oxidative stress; whether the two conditions would show additive or interactive effects on the severity of depressive symptoms, and whether this is related to the level of oxidative stress in the CNS is unknown. 123 participants were evaluated, which included 41 HIV-seronegative subjects without substance use disorders (Control), 25 with recent (
Source: Journal of NeuroImmune Pharmacology - January 10, 2015 Category: Drugs & Pharmacology Source Type: research

PPARα Signaling in the Hippocampus: Crosstalk Between Fat and Memory
Abstract Major functions of the hippocampus are to generate, organize and store memory. This is a complex process, which is orchestrated by a group of molecules, called plasticity-related molecules. To control these various plasticity-related molecules at the transcriptional level, we have been endowed with cAMP response element-binding protein (CREB), also known as a master regulator of memory. Interestingly, we have seen that this master regulator is regulated at the transcriptional level in the hippocampus by peroxisome proliferator-activated receptor α (PPARα), a nuclear hormone receptor family tra...
Source: Journal of NeuroImmune Pharmacology - January 10, 2015 Category: Drugs & Pharmacology Source Type: research

Heroin Use Promotes HCV Infection and Dysregulates HCV-Related Circulating microRNAs
Abstract Hepatitis C virus (HCV) infection is common among injection drug users (IDUs). There is accumulating evidence that circulating microRNAs (miRNAs) are associated with HCV infection and disease progression. The present study was undertaken to determine the in vivo impact of heroin use on HCV infection and HCV-related circulating miRNA expression. Using the blood specimens from four groups of the study subjects (HCV-infected individuals, heroin users with/without HCV infection, and healthy volunteers), we found that HCV-infected heroin users had significantly higher viral load than HCV-infected non-heroin us...
Source: Journal of NeuroImmune Pharmacology - January 8, 2015 Category: Drugs & Pharmacology Source Type: research

Amphiphilic Cationic Nanogels as Brain-Targeted Carriers for Activated Nucleoside Reverse Transcriptase Inhibitors
Abstract Progress in AIDS treatment shifted emphasis towards limiting adverse effects of antiviral drugs while improving the treatment of hard-to-reach viral reservoirs. Many therapeutic nucleoside reverse transcriptase inhibitors (NRTI) have a limited access to the central nervous system (CNS). Increased NRTI levels induced various complications during the therapy, including neurotoxicity, due to the NRTI toxicity to mitochondria. Here, we describe an innovative design of biodegradable cationic cholesterol-ε-polylysine nanogel carriers for delivery of triphosphorylated NRTIs that demonstrated high anti-HI...
Source: Journal of NeuroImmune Pharmacology - January 5, 2015 Category: Drugs & Pharmacology Source Type: research

Neuroprotection in Experimental Autoimmune Encephalomyelitis and Progressive Multiple Sclerosis by Cannabis-Based Cannabinoids
Abstract Multiple sclerosis (MS) is the major immune-mediated, demyelinating, neurodegenerative disease of the central nervous system. Compounds within cannabis, notably Δ9-tetrahydrocannabinol (Δ9-THC) can limit the inappropriate neurotransmissions that cause MS-related problems and medicinal cannabis is now licenced for the treatment of MS symptoms. However, the biology indicates that the endocannabinoid system may offer the potential to control other aspects of disease. Although there is limited evidence that the cannabinoids from cannabis are having significant immunosuppressive activities tha...
Source: Journal of NeuroImmune Pharmacology - December 23, 2014 Category: Drugs & Pharmacology Source Type: research

An Infectious Murine Model for Studying the Systemic Effects of Opioids on Early HIV Pathogenesis in the Gut
In this study, the systemic effects of EcoHIV infection, a modified HIV which can infect mouse cells, are examined in conjunction with morphine. EcoHIV infection with opioid treatment induced bacterial translocation from the lumen of the gut into systemic compartments such as liver, which is similar to observations in human patients with LPS. Bacterial translocation corresponds with alterations in gut morphology, disorganization of the tight junction protein occludin, and a concurrent increase in systemic inflammation in both IL-6 and TNFα. Long term infection also had increased expression of inflammatory cytoki...
Source: Journal of NeuroImmune Pharmacology - December 12, 2014 Category: Drugs & Pharmacology Source Type: research

Potential Neuroprotective Activity of Ginseng in Parkinson’s Disease: A Review
Abstract Parkinson’s disease is a chronic, multifactorial and progressive neurologic condition that affects around six million people worldwide, normally over 60 years of age, and is characterized by neurodegeneration of dopaminergic neurons in the substantia nigra. The species of the genus Panax, popularly named as “Ginseng”, are widely used as herbal remedies for their multiple beneficial effects, including their neurotherapeutic efficacies as protectors against major neurodegenerative diseases. The current review aims to report major findings and current knowledge on Ginseng and its major...
Source: Journal of NeuroImmune Pharmacology - October 29, 2014 Category: Drugs & Pharmacology Source Type: research

Domain Structure and Conformational Changes in rat K V 2.1 ion Channel
Abstract Voltage-gated potassium Kv2.1 channels are widely distributed in the central nervous system, specifically in neuroendocrine and endocrine cells. Their cytoplasmic C-termini are large and carry out many important functions. Here we provide the first direct structural evidence that each C-terminal part within the Kv2.1 ion channel is formed by two distinct domains (Kv2 and CTA). We expressed and purified two C-terminal truncation mutants of a rat Kv2.1 channel, lacking the entire C-termini or the CTA domain. Single particle electron microscopy was used to obtain three-dimensional reconstructions of purifie...
Source: Journal of NeuroImmune Pharmacology - October 23, 2014 Category: Drugs & Pharmacology Source Type: research

IL-17A Induces MIP-1α Expression in Primary Astrocytes via Src/MAPK/PI3K/NF-kB Pathways: Implications for Multiple Sclerosis
Abstract Neuroinflammation plays critical roles in multiple sclerosis (MS). In addition to the part played by the lymphocytes, the underlying mechanisms could, in part, be also attributed to activation mediated by astrocytes. Macrophage inflammatory protein-1α (MIP-1α) has been implicated in a number of pathological conditions, specifically attributable to its potent chemottractant effects. Its modulation by IL-17, however, has received very little attention. In the present study, we demonstrated IL-17-mediated induction of MIP-1α in rat primary astroctyes through its binding to the cognate IL-1...
Source: Journal of NeuroImmune Pharmacology - October 23, 2014 Category: Drugs & Pharmacology Source Type: research

HIV-1 Transgenic Female Rat: Synaptodendritic Alterations of Medium Spiny Neurons in the Nucleus Accumbens
In this study, adult female HIV-1 Tg rats and F344 control rats had similar growth rates, estrous cyclicity and startle reflex inhibition to a visual prepulse stimulus. Medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) were ballistically-labeled utilizing the indocarbocyanine dye DiI. The branching complexity of MSNs in the NAcc was significantly decreased in HIV-1 Tg rats, relative to controls; moreover, the shorter length and decreased volume of dendritic spines, but unchanged head diameter, in HIV-1 Tg rats suggested a reduction of longer spines and an increase in shorter, less projected spines, indicating a p...
Source: Journal of NeuroImmune Pharmacology - October 23, 2014 Category: Drugs & Pharmacology Source Type: research

The Calcineurin Inhibitor Ascomicin Interferes with the Early Stage of the Epileptogenic Process Induced by Latrunculin A Microperfusion in Rat Hippocampus
Abstract Latrunculin A microperfusion in rat hippocampus has shown to be an effective model of acute and chronic seizures for neurochemical studies. The intervention over early synaptic plasticity changes after the epileptogenesis onset represents a big challenge on the design of a suitable therapy to impair the epilepsy development. We previously suggested that receptor location might be essential for controlling neuronal excitability, and that disruption of local cytoskeletal dynamics followed by drastic changes in the synaptic/extrasynaptic ratio of NMDA, AMPA receptors and their subsequent downstream signalli...
Source: Journal of NeuroImmune Pharmacology - October 23, 2014 Category: Drugs & Pharmacology Source Type: research

Pro-Inflammatory Interferon Gamma Signaling is Directly Associated with Stroke Induced Neurodegeneration
This study was designed to determine the role of IFNγ signaling in the inflammatory response following MCAO. Expression of IP-10 increased in the brain and the spleen following MCAO. Splenectomy inhibited the increase of IP-10 in the brain post-MCAO, while recombinant IFNγ administration to splenectomized rats returned IP-10 levels in the brain to levels found in rats after MCAO only. Systemic administration of an IFNγ neutralizing antibody to MCAO-treated rats reduced infarct volume and IP-10 levels in the brain. T cell infiltration was reduced in the MCAO-damaged brains of IFNγ antibody-treated an...
Source: Journal of NeuroImmune Pharmacology - October 23, 2014 Category: Drugs & Pharmacology Source Type: research

On the Connection Between Autoimmunity, tic Disorders and Obsessive-Compulsive Disorders: A Meta-Analysis on Anti-Streptolysin O Titres
Abstract Anti-streptolysin O (ASO) titration is useful in the context of autoimmune pathologies, including specific cases of tic and obsessive-compulsive disorders occurring after streptococcal infections. There is currently a lack of consensus on the use of ASO titres; therefore we performed a meta-analysis to systematise available data and clarify the role of ASO titres in the context of neuropsychiatric disorders. A meta-analysis was performed on ASO titration in neuropsychiatric patients, including tic disorders and obsessive-compulsive disorders. Included studies reported numbers of positive subjects, depend...
Source: Journal of NeuroImmune Pharmacology - October 23, 2014 Category: Drugs & Pharmacology Source Type: research

Therapeutic Efficacy of Neuro AiD™ (MLC 601), a Traditional Chinese Medicine, in Experimental Traumatic Brain Injury
In this study we used a controlled fluid percussion injury model of TBI in the rat to determine whether early (4 h post-injury) or late (4 days post-injury) treatment with MLC 601, a Traditional Chinese Medicine, would affect microglial activation and improve recovery. MLC 601 was chosen for this study because its herbal component MLC 901 was beneficial in treating TBI in rats. Herein, rats with induced TBI were treated with MLC 601 (0.2–0.8 mg/kg) 1 h (early treatment) or 4 day post-injury (late treatment) and then injected once daily for consecutive 2 days. Acute neurological and motor...
Source: Journal of NeuroImmune Pharmacology - October 21, 2014 Category: Drugs & Pharmacology Source Type: research

Differential Neuroprotective and Anti-Inflammatory Effects of L-Type Voltage Dependent Calcium Channel and Ryanodine Receptor Antagonists in the Substantia Nigra and Locus Coeruleus
Abstract Neuroinflammation and degeneration of catecholaminergic brainstem nuclei occur early in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Neuroinflammation increases levels of pro-inflammatory cytokines and reactive oxygen species which can alter neuronal calcium (Ca+2) homoeostasis via L-type voltage dependent calcium channels (L-VDCCs) and ryanodine receptors (RyRs). Alterations in Ca+2 channel activity in the SN and LC can lead to disruption of normal pacemaking activity in these areas, contributing to behavioral deficits. Here, we utilized an in vivo model of ...
Source: Journal of NeuroImmune Pharmacology - October 16, 2014 Category: Drugs & Pharmacology Source Type: research

Plasma Cytokine Levels are Related to Brain Volumes in HIV-infected Individuals
We examined 74 medically stable HIV-infected individuals using T1-weighted MRI. Volumes of the cortical grey matter (GM), white matter (WM), caudate, putamen, globus pallidus, thalamus, hippocampus, amygdala, and ventricles were derived using automated parcellation. A panel of plasma cytokines was measured using multiplexed bead array immunoassay. A model selection algorithm was used to select the combination of clinical and cytokine markers that best predicted each brain volumetric measure in a series of linear regression models. Higher CD4 nadir, shorter HIV infection duration, and antiretroviral treatment were significa...
Source: Journal of NeuroImmune Pharmacology - October 1, 2014 Category: Drugs & Pharmacology Source Type: research

Domain Structure and Conformational Changes in rat KV2.1 ion Channel
Abstract Voltage-gated potassium Kv2.1 channels are widely distributed in the central nervous system, specifically in neuroendocrine and endocrine cells. Their cytoplasmic C-termini are large and carry out many important functions. Here we provide the first direct structural evidence that each C-terminal part within the Kv2.1 ion channel is formed by two distinct domains (Kv2 and CTA). We expressed and purified two C-terminal truncation mutants of a rat Kv2.1 channel, lacking the entire C-termini or the CTA domain. Single particle electron microscopy was used to obtain three-dimensional reconstructions of purified...
Source: Journal of NeuroImmune Pharmacology - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

Dynamic Nature of the p75 Neurotrophin Receptor in Response to Injury and Disease
Abstract Neurotrophins and their respective tropomyosin related kinase (Trk) receptors (TrkA, TrkB, and TrkC) and the p75 neurotrophin receptor (p75NTR) play a fundamental role in the development and maintenance of the nervous system making them important targets for treatment of neurodegenerative diseases. Whereas Trk receptors are directly activated by specific neurotrophins, the p75NTR is a multifunctional receptor that exerts its effects via heterodimeric interactions with TrkA, TrkB, TrkC, sortilin or the Nogo receptor to regulate a wide array of cellular functions. By partnering with different receptors the ...
Source: Journal of NeuroImmune Pharmacology - September 20, 2014 Category: Drugs & Pharmacology Source Type: research

Cocaine Potentiates Cathepsin B Secretion and Neuronal Apoptosis from HIV-Infected Macrophages
Abstract Substance abuse is a risk factor for HIV infection and progression to AIDS. Recent evidence establishes that cocaine use promotes brain perivascular macrophage infiltration and microglia activation. The lysosomal protease cathepsin B is increased in monocytes from patients with HIV dementia and its secretion induces 10–15 % of neurotoxicity. Here we asked if cocaine potentiates cathepsin B secretion from HIV-infected monocyte-derived macrophages (MDM) and its effect in neuronal apoptosis. Samples of plasma, CSF, and post-mortem brain tissue from HIV positive patients that used cocaine were test...
Source: Journal of NeuroImmune Pharmacology - September 11, 2014 Category: Drugs & Pharmacology Source Type: research

Diazoxide Attenuates Autoimmune Encephalomyelitis and Modulates Lymphocyte Proliferation and Dendritic Cell Functionality
Abstract Activation of mitochondrial ATP-sensitive potassium (KATP) channels is postulated as an effective mechanism to confer cardio and neuroprotection, especially in situations associated to oxidative stress. Pharmacological activation of these channels inhibits glia-mediated neuroinflammation. In this way, diazoxide, an old-known mitochondrial KATP channel opener, has been proposed as an effective and safe treatment for different neurodegenerative diseases, demonstrating efficacy in different animal models, including the experimental autoimmune encephalomyelitis (EAE), an animal model for Multiple Sclerosis. ...
Source: Journal of NeuroImmune Pharmacology - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

Enhanced Humoral Immunity in Mice Lacking CB1 and CB2 Receptors (Cnr1 −/− /Cnr2 −/− Mice) is not Due to Increased Splenic Noradrenergic Neuronal Activity
Abstract Peripheral sympathetic noradrenergic neurons originating in the celiac mesenteric plexus have axons that terminate in close proximity to antibody-producing B cells in the spleen. Norepinephrine (NE) released from these neurons is reported to augment antibody production in response to an immune challenge via an action at the β2-adrenergic receptor (β2AR). Cannabinoids are immunosuppressive, and mice lacking CB1 and CB2 receptors (Cnr1 −/− /Cnr2 −/− mice) have augmented cell-mediated immune ...
Source: Journal of NeuroImmune Pharmacology - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

PET imaging in multiple sclerosis
Abstract Positron emission tomography (PET) is a non-invasive technique for quantitative imaging of biochemical and physiological processes in animals and humans. PET uses probes labeled with a radioactive isotope, called PET tracers, which can bind to or be converted by a specific biological target and thus can be applied to detect and monitor different aspects of diseases. The number of applications of PET imaging in multiple sclerosis is still limited. Clinical studies using PET are basically focused on monitoring changes in glucose metabolism and the presence of activated microglia/macrophages in sclerotic le...
Source: Journal of NeuroImmune Pharmacology - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

Modeling Deficits in Attention, Inhibition, and Flexibility in HAND
Abstract Nearly half of all HIV-1-positive individuals on combination antiretroviral therapy (cART) are afflicted with HIV-1-associated neurocognitive disorders (HAND). The most prevalent cognitive deficits observed in the cART era are those of attention and executive function. Presently, we sought to model deficits in attention and core components of executive function (inhibition, flexibility, and set-shifting) observed in HAND using the HIV-1 transgenic (Tg) rat, which expresses 7 of the 9 HIV-1 genes. Ovariectomized female Fischer HIV-1 Tg and non-transgenic control rats (ns = 39–43) were ...
Source: Journal of NeuroImmune Pharmacology - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

Mechanisms Underlying the Effect of Acupuncture on Cognitive Improvement: A Systematic Review of Animal Studies
Abstract Acupuncture has been reported to be beneficial in treating cognitive impairment in various pathological conditions. This review describes the effort to understand the signaling pathways that underlie the acupunctural therapeutic effect on cognitive function. We searched the literature in 12 electronic databases from their inception to November 2013, with full text available and language limited to English. Twenty-three studies were identified under the selection criteria. All recruited animal studies demonstrate a significant positive effect of acupuncture on cognitive impairment. Findings suggest acupun...
Source: Journal of NeuroImmune Pharmacology - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

Angiotensin IV is Induced in Experimental Autoimmune Encephalomyelitis but Fails to Influence the Disease
Abstract In multiple sclerosis (MS) and its corresponding animal models, over-activity of the renin-angiotensin system (RAS) has been reported and pharmacological RAS blockade exerts beneficial effects. The RAS generates a number of bioactive angiotensins, thereby primarily regulating the body’s sodium homeostasis and blood pressure. In this regard, angiotensin IV (AngIV), a metabolite of the RAS has been shown to modulate inflammatory responses. Here we studied potential implications of AngIV signalling in myelin oligodendrocyte glycoprotein (MOG) peptide induced murine experimental autoimmune encephalomye...
Source: Journal of NeuroImmune Pharmacology - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

Cinnamon Treatment Upregulates Neuroprotective Proteins Parkin and DJ-1 and Protects Dopaminergic Neurons in a Mouse Model of Parkinson’s Disease
Abstract Upregulation and/or maintenance of Parkinson’s disease (PD)-related beneficial proteins such as Parkin and DJ-1 in astrocytes during neurodegenerative insults may have therapeutic efficacy in PD. Cinnamon is a commonly used natural spice and flavoring material throughout the world. Here we have explored a novel use of cinnamon in upregulating Parkin and DJ-1 and protecting dopaminergic neurons in MPTP mouse model of PD. Recently we have delineated that oral feeding of cinnamon (Cinnamonum verum) powder produces sodium benzoate (NaB) in blood and brain of mice. Proinflammatory cytokine IL-1β de...
Source: Journal of NeuroImmune Pharmacology - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

Epigenetic Modification of the FoxP3 TSDR in HAM/TSP Decreases the Functional Suppression of Tregs
Abstract HTLV-1 is a human retrovirus that is associated with the neuroinflammatory disorder HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). In these patients, HTLV-1 is primarily found in the CD4+CD25+ T cell subset (Regulatory T cells:Tregs), which is responsible for peripheral immune tolerance and is known to be dysfunctional in HAM/TSP. Recent evidence suggests that FoxP3 expression and function is determined epigenetically through DNA demethylation in the Treg-specific demethylated region (TSDR). We analyzed the methylation of the TSDR in PBMCs, CD4+ T cells, and CD4+CD25+ T cells from n...
Source: Journal of NeuroImmune Pharmacology - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

β-arrestin 2 mediates the anti-inflammatory effects of fluoxetine in lipopolysaccharide-stimulated microglial cells
Abstract Recent evidence has suggested that microglial activation plays an important role in the pathogenesis of depression. Activated microglia can secrete various pro-inflammatory cytokines, which may contribute to the development and maintenance of depression. Thus, inhibition of microglial activation may have a therapeutic benefit in the treatment of depression. In the present study, we found that fluoxetine significantly inhibited lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α), interleukin- 6 (IL-6) and nitric oxide (NO) and reduced the phosphorylation of transformin...
Source: Journal of NeuroImmune Pharmacology - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

Role of HIV in Amyloid Metabolism
Abstract HIV infection has changed from an acute devastating disease to a more chronic illness due to combination anti-retroviral treatment (cART). In the cART era, the life expectancy of HIV-infected (HIV+) individuals has increased. More HIV + individuals are aging with current projections suggesting that 50 % of HIV + individuals will be over 50 years old by 2015. With advancing age, HIV + individuals may be at increased risk of developing other potential neurodegenerative disorders [especially Alzheimer’s disease (AD)]. Pathology studies have shown tha...
Source: Journal of NeuroImmune Pharmacology - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

Target Engagement Analysis and Link to Pharmacodynamic Endpoint for a Novel Class of CNS-penetrant and Efficacious p38α MAPK Inhibitors
We report here more detailed analyses of MW181 target engagement and specific linkage to the downstream increase in glia proinflammatory cytokine production. In vivo validation included demonstration that oral administration of MW181 suppresses lipopolysaccharide-induced increases in mouse brain IL-1β, TNFα, IL-6, IL-10, and CXCL1 but not in a drug-resistant p38α MAPK mutant mouse. (Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

2-Cyclopropylimino-3-Methyl-1,3-Thiazoline Hydrochloride Inhibits Microglial Activation by Suppression of Nuclear Factor-Kappa B and Mitogen-Activated Protein Kinase Signaling
Abstract The activation of microglia is crucially associated with the neurodegeneration observed in many neuroinflammatory pathologies, including multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease. Therefore, the inhibition of microglial activation may alleviate certain neurodegenerative processes. We previously demonstrated the protective actions of a new drug, 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride (KHG26377), against glutamate-induced excitotoxicity and ischemic neuronal damage in in vivo rat brain study. The current investigation explored the possible mechanisms und...
Source: Journal of NeuroImmune Pharmacology - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

Cannabinoid Receptor-2 and HIV-Associated Neurocognitive Disorders
Abstract Despite the wide spread use of highly active antiretroviral therapy (HAART), mild forms of HIV-associated neuro cognitive disorders (HAND) remain commonplace. HAART treated patients now show low levels of viremia and more subtle yet biologically important signs of brain macrophage and microglial activation. Adjunctive therapeutic strategies are required to eliminate HIV-1 infection and suppress immune activation and its associated neuroinflammation. In this regard, cannabinoid receptor-2(CB2) activation is a promising means to attenuate HAND by inhibiting HIV replication, down regulating inflammation, an...
Source: Journal of NeuroImmune Pharmacology - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

Expression of the Mannose Receptor CD206 in HIV and SIV Encephalitis: A Phenotypic Switch of Brain Perivascular Macrophages with Virus Infection
We examined the expression of the mannose receptor CD206 by perivascular macrophages (PVM) in normal human and monkey brains and in brains of HIV-infected humans and of monkeys infected with simian immunodeficiency virus (SIV). Depletion of brain PVM in SIV-infected monkeys by intrathecal injection of liposome-encapsulated bisphosphonates eliminated CD206-expressing cells in the brain, confirming their perivascular location and phagocytic capacity. In vivo labeling with bromodeoxyuridine in normal uninfected and SIV-infected macaques in combination with CD206 immunostaining revealed a CD206+-to-CD206– shift within pr...
Source: Journal of NeuroImmune Pharmacology - August 22, 2014 Category: Drugs & Pharmacology Source Type: research

P2X4 Receptor Regulates Alcohol-Induced Responses in Microglia
Abstract Mounting evidence indicates that alcohol-induced neuropathology may result from multicellular responses in which microglia cells play a prominent role. Purinergic receptor signaling plays a key role in regulating microglial function and, more importantly, mediates alcohol-induced effects. Our findings demonstrate that alcohol increases expression of P2X4 receptor (P2X4R), which alters the function of microglia, including calcium mobilization, migration and phagocytosis. Our results show a significant up-regulation of P2X4 gene expression as analyzed by real-time qPCR (***p 
Source: Journal of NeuroImmune Pharmacology - August 20, 2014 Category: Drugs & Pharmacology Source Type: research

Emerging Roles of Pericytes in the Regulation of the Neurovascular Unit in Health and Disease
Abstract Pericytes of the central nervous system (CNS) are uniquely positioned within a multicellular structure termed the neurovascular unit (NVU) to provide crucial support to blood brain barrier (BBB) formation, maintenance, and stability. Numerous CNS diseases are associated with some aspect of BBB dysfunction. A dysfunction can manifest as one or multiple disruptions to any of the following barriers: physical, metabolic, immunological and transport barrier. A breach in the BBB can notably result in BBB hyper-permeability, endothelial activation and enhanced immune-endothelial interaction. How the BBB is regul...
Source: Journal of NeuroImmune Pharmacology - August 14, 2014 Category: Drugs & Pharmacology Source Type: research

3,4-Methylenedioxymethamphetamine (MDMA – Ecstasy) Decreases Neutrophil Activity Through the Glucocorticoid Pathway and Impairs Host Resistance to Listeria Monocytogenes Infection in Mice
Abstract Ecstasy is the popular name of the abuse drug 3,4-methylenedioxymethamphetamine (MDMA) that decreases immunity in animals. The mechanisms that generate such alterations are still controversial. Seven independent pharmacological approaches were performed in mice to identify the possible mechanisms underlying the decrease of neutrophil activity induced by MDMA and the possible effects of MDMA on host resistance to Listeria monocytogenes. Our data showed that MDMA (10 mg kg−1) administration decreases NFκB expression in circulating neutrophils. Metyrapone or RU-486 administration prior to MD...
Source: Journal of NeuroImmune Pharmacology - August 12, 2014 Category: Drugs & Pharmacology Source Type: research