A Novel Aβ B-Cell Epitope Vaccine (rCV01) for Alzheimer’s Disease Improved Synaptic and Cognitive Functions in 3 × Tg-AD Mice
Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a progressive amyloid-β accumulation, loss of cognitive abilities, and synaptic alterations. Given the remarkable recovery of cognition in AD models of targeting-Aβ immunotherapy, we sought to determine the molecular correlate(s) associated with improvement. We evaluated the efficacy of a recombinant chimeric 6Aβ15-T antigen formulated with alum adjuvant as a novel Aβ B-cell epitope vaccine (rCV01) in 3 × Tg-AD mice. rCV01 elicited robust Th2-polarized Aβ-specific antibodies without aut...
Source: Journal of NeuroImmune Pharmacology - May 5, 2016 Category: Drugs & Pharmacology Source Type: research

Modulation Effect of HIV-1 Viral Proteins and Nicotine on Expression of the Immune-Related Genes in Brain of the HIV-1 Transgenic Rats
Abstract The human immunodeficiency virus-1 transgenic (HIV-1Tg) rat is a non-infectious rodent model for HIV-1 infection which develops altered immune-responses similar to those in persons infected with HIV-1. HIV-1Tg and F344 rats respond significantly different to morphine, ethanol, nicotine and other psychostimulants, although the molecular mechanisms underlying these differences remain largely undetermined. Here, we compared expression of 52 immune-related genes in the prefrontal cortex (PFC), nucleus accumbens (NAc), and ventral tegmental area (VTA) of HIV-1Tg and F344 rats treated with either nicotine (0.4&...
Source: Journal of NeuroImmune Pharmacology - May 4, 2016 Category: Drugs & Pharmacology Source Type: research

Mitochondrial Quality Control Proteases in Neuronal Welfare
Abstract The functional integrity of mitochondria is a critical determinant of neuronal health and compromised mitochondrial function is a commonly recognized factor that underlies a plethora of neurological and neurodegenerative diseases. Metabolic demands of neural cells require high bioenergetic outputs that are often associated with enhanced production of reactive oxygen species. Unopposed accumulation of these respiratory byproducts over time leads to oxidative damage and imbalanced protein homeostasis within mitochondrial subcompartments, which in turn may result in cellular demise. The post-mitotic nature o...
Source: Journal of NeuroImmune Pharmacology - May 2, 2016 Category: Drugs & Pharmacology Source Type: research

Brain Microstructure and Impulsivity Differ between Current and Past Methamphetamine Users
Abstract Methamphetamine (Meth) use disorder continues to be highly prevalent worldwide. Meth users have higher impulsivity and brain abnormalities that may be different between current and past Meth users. The current study assessed impulsivity and depressive symptoms in 94 participants (27 current Meth users, 32 past Meth users and 35 non-drug user controls). Additionally, brain microstructure was assessed using diffusion tensor imaging (DTI); fractional anisotropy (FA) and mean diffusivity (MD) were assessed in the striatum, and FA, MD, radial and axial diffusivity were quantified in five white matter structure...
Source: Journal of NeuroImmune Pharmacology - April 30, 2016 Category: Drugs & Pharmacology Source Type: research

Persistent Microstructural Deficits of Internal Capsule in One-Year Abstinent Male Methamphetamine Users: a Longitudinal Diffusion Tensor Imaging Study
Abstract White matter (WM) alterations have been reported in methamphetamine (MA) users. However, knowledge about longitudinal changes in WM during abstinence from MA remains unknown. The present study aimed to examine how WM changes in long-term MA abstinent, in particular, whether the WM deficits would recover as the duration of abstinence extended. Twenty male MA dependent individuals and 19 healthy controls (HCs) were recruited and participated in both clinical assessments and diffusion tensor imaging (DTI) scans. The MA group underwent two DTI scans, a baseline scan with a duration of abstinence of 6.4 m...
Source: Journal of NeuroImmune Pharmacology - April 26, 2016 Category: Drugs & Pharmacology Source Type: research

Chronic Δ 9 -Tetrahydrocannabinol Administration Reduces IgE + B Cells but Unlikely Enhances Pathogenic SIV mac251 Infection in Male Rhesus Macaques of Chinese Origin
Abstract Delta9-tetrahydrocannabinol (Δ9-THC) is the major psychoactive component of the cannabis plant. Δ9-THC has been used in the active ingredient of Marinol as an appetite stimulant for AIDS patients. Its impact on progression of HIV-1 infection, however, remains debatable. Previous studies indicated that Δ9-THC administration enhanced HIV-1 infection in huPBL-SCID mice but seemingly decreased early mortality in simian immunodeficiency virus (SIV) infected male Indian-derived rhesus macaques. Here, we determine the chronic effect of Δ9-THC administration using 0.32 mg/kg or p...
Source: Journal of NeuroImmune Pharmacology - April 25, 2016 Category: Drugs & Pharmacology Source Type: research

Stem Cell Factor (SCF) is a putative biomarker of antidepressant response
Abstract Growth factors involved in neurogenesis and neuroplasticity could play a role in biological processes that drive depression recovery. Combined total sleep deprivation and morning light therapy (TSD + LT) can acutely reverse depressive symptoms, thus allowing to investigate the neurobiological correlates of antidepressant response. We tested if changes on plasma levels of Brain Derived Neurotrophic Factor (BDNF), S100 calcium binding protein B (S100-B), Stem Cell Factor (SCF), Insulin-like Growth Factor-Binding Protein 2 (IGFBP-2), Epidermal Growth Factor (EGF), Platelet-Derived Growth Factor-BB ...
Source: Journal of NeuroImmune Pharmacology - April 23, 2016 Category: Drugs & Pharmacology Source Type: research

Decreased Expression of Plasma MicroRNA in Patients with Methamphetamine (MA) Use Disorder
Abstract Recent research have revealed that circulating miRNAs may offer noninvasive biomarkers for human disease, offering the prospect for earlier diagnosis, and improved precision of diagnoses. The diagnoses of drug use disorders is still mainly based on subjective report and no objective biomarkers available. Many animal and cell studies found that miRNAs were involved in substance use disorders, including alcohol, morphine, cocaine and amphetamine use disorders. However, no study on circulating miRNAs for drug use disorders so far. We investigated the differential expression of plasma miRNAs in 124 patients w...
Source: Journal of NeuroImmune Pharmacology - April 23, 2016 Category: Drugs & Pharmacology Source Type: research

B-Cell Depletion Reduces the Maturation of Cerebral Cavernous Malformations in Murine Models
Abstract Cerebral cavernous malformations (CCMs) are relatively common vascular malformations, characterized by increased Rho kinase (ROCK) activity, vascular hyper-permeability and the presence of blood degradation products including non-heme iron. Previous studies revealed robust inflammatory cell infiltration, selective synthesis of IgG, in situ antigen driven B-cell clonal expansion, and deposition of immune complexes and complement proteins within CCM lesions. We aimed to evaluate the impact of suppressing the immune response on the formation and maturation of CCM lesions, as well as lesional iron deposition ...
Source: Journal of NeuroImmune Pharmacology - April 16, 2016 Category: Drugs & Pharmacology Source Type: research

Polymorphism of Kynurenine Pathway-Related Genes, Kynurenic Acid, and Psychopathological Symptoms in HIV
Abstract HIV-infection is associated with neuroinflammation and greater psychopathological symptoms, which may be mediated by imbalances in the kynurenic pathway (KP). Two key KP enzymes that catabolize kynurenine include kynurenine-aminotransferase II (KATII), which yields antioxidative kynurenine acid [KYNA] in astrocytes, and kynurenine-3-monooxygenase (KMO), which produces neurotoxic metabolites in microglia. The relationships between polymorphisms in KMO and KATII, psychopathological symptoms, and cerebrospinal fluid (CSF) [KYNA] were evaluated in subjects with and without HIV-infection. Seventy-two HIV-posit...
Source: Journal of NeuroImmune Pharmacology - April 12, 2016 Category: Drugs & Pharmacology Source Type: research

Cerebrospinal Fluid Biomarkers of Simian Immunodeficiency Virus Encephalitis
Abstract Antiretroviral therapy has led to increased survival of HIV-infected patients but also increased prevalence of HIV-associated neurocognitive disorders. We previously identified YKL40 as a potential cerebrospinal fluid (CSF) biomarker of lentiviral central nervous system (CNS) disease in HIV-infected patients and in the macaque model of HIV encephalitis. The aim of this study was to define the specificity and sensitivity along with the predictive value of YKL40 as a biomarker of encephalitis and to assess its relationship to CSF viral load. CSF YKL40 and SIV RNA concentrations were analyzed over the course...
Source: Journal of NeuroImmune Pharmacology - April 8, 2016 Category: Drugs & Pharmacology Source Type: research

Effects of Morphine on Behavioral Task Performance in SIV-Infected Rhesus Macaques
Abstract The abuse of opiates such as morphine in synergy with HIV infection not only exacerbates neuropathogenesis but significantly impacts behavioral attributes in HIV infected subjects. Thus, the goal of the current study was to characterize behavioral perturbations in rhesus macaques subjected to chronic morphine and SIV infection. Specifically, we assessed three behavioral tasks: motor skill (MS), forelimb force (FFT) and progressive ratio (PR) tasks. After collecting baseline control data (44 weeks) and data during the morphine-only dependency period (26 weeks), a subset of animals were productive...
Source: Journal of NeuroImmune Pharmacology - April 2, 2016 Category: Drugs & Pharmacology Source Type: research

HIV-1 Tat and Cocaine Impair Survival of Cultured Primary Neuronal Cells via a Mitochondrial Pathway
Abstract Addictive stimulant drugs, such as cocaine, are known to increase the risk of exposure to HIV-1 infection and hence predispose towards the development of AIDS. Previous findings suggested that the combined effect of chronic cocaine administration and HIV-1 infection enhances cell death. Neuronal survival is highly dependent on the health of mitochondria providing a rationale for assessing mitochondrial integrity and functionality following cocaine treatment, either alone or in combination with the HIV-1 viral protein Tat, by monitoring ATP release and mitochondrial membrane potential (ΔΨm). Our ...
Source: Journal of NeuroImmune Pharmacology - March 31, 2016 Category: Drugs & Pharmacology Source Type: research

A Perspective on Opioid Pharmacotherapy: Where We Are and How We Got Here
Abstract Four decades of concerted pharmacotherapy research has netted us three medications approved for the treatment of opioid addiction. The clinical pharmacology, safety, efficacy, and clinical use of these medications are familiar to most clinical researchers and clinicians in addiction medicine. Less common is an understanding of the social and political forces behind the choice of these particular agents for their development and how these forces continue to influence how clinicians interact with patients who have opioid use disorder. This review brings into focus those forces and puts into context how we c...
Source: Journal of NeuroImmune Pharmacology - March 23, 2016 Category: Drugs & Pharmacology Source Type: research

Drug Abuse, HIV, and HCV in Asian Countries
Abstract Drug abuse and co-occurring infections are associated with significant morbidity and mortality. Asian countries are particularly vulnerable to the deleterious consequences of these risks/problems, as they have some of the highest rates of these diseases. This review describes drug abuse, HIV, and hepatitis C (HCV) in Asian countries. The most commonly used illicit drugs include opioids, amphetamine-type stimulants (ATS), cannabis, and ketamine. Among people who inject drugs, HIV rates range from 6.3 % in China to 19 % in Malaysia, and HCV ranges from 41 % in India and Taiwan to 74 % in...
Source: Journal of NeuroImmune Pharmacology - March 21, 2016 Category: Drugs & Pharmacology Source Type: research

Cannabinoids Occlude the HIV-1 Tat-Induced Decrease in GABAergic Neurotransmission in Prefrontal Cortex Slices
Abstract In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is now considered a chronic disease that specifically targets the brain and causes HIV-1-associated neurocognitive disorders (HAND). Endocannabinoids exhibit neuroprotective and anti-inflammatory properties in several central nervous system (CNS) disease models, but their effects in HAND are poorly understood. To address this issue, whole-cell recordings were performed on young (14–24 day old) C57BL/6J mice. We investigated the actions of the synthetic cannabinoid WIN55,212-2 (1 μM) and the endo...
Source: Journal of NeuroImmune Pharmacology - March 18, 2016 Category: Drugs & Pharmacology Source Type: research

Abstracts of the 22nd Scientific Conference of the Society on Neuroimmune Pharmacology
(Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - March 18, 2016 Category: Drugs & Pharmacology Source Type: research

Chemokine CCL2 enhances NMDA receptor-mediated excitatory postsynaptic current in rat hippocampal slices-a potential mechanism for HIV-1-associated neuropathy?
Abstract Human immunodeficiency virus type 1 (HIV-1)-infected mononuclear phagocytes (brain macrophages and microglial cells) release proinflammatory cytokines and chemokines. Elevated levels of chemokine CC motif ligand 2 (CCL2, known previously as monocyte chemoattractant protein-1) have been detected in serum and cerebrospinal fluid (CSF) of HIV-1-infected individuals and the raised CCL2 in the CSF correlates with HIV-1-associated neurocognitive disorders. To understand how elevated CCL2 induces HIV-1-associated neuropathy, we studied effects of CCL2 on excitatory postsynaptic current (EPSCs) in the CA1 region ...
Source: Journal of NeuroImmune Pharmacology - March 11, 2016 Category: Drugs & Pharmacology Source Type: research

The 22nd Scientific Conference of the Society on Neuroimmune Pharmacology
(Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - March 11, 2016 Category: Drugs & Pharmacology Source Type: research

Dexmedetomidine Postconditioning Reduces Brain Injury after Brain Hypoxia-Ischemia in Neonatal Rats
Abstract Perinatal asphyxia can lead to death and severe disability. Brain hypoxia-ischemia (HI) injury is the major pathophysiology contributing to death and severe disability after perinatal asphyxia. Here, seven-day old Sprague-Dawley rats were subjected to left brain HI. Dexmedetomidine was given intraperitoneally after the brain HI. Yohimbine or atipamezole, two α2 adrenergic receptor antagonists, were given 10 min before the dexmedetomidine injection. Neurological outcome was evaluated 7 or 28 days after the brain HI. Frontal cerebral cortex was harvested 6 h after the brain HI. Left bra...
Source: Journal of NeuroImmune Pharmacology - March 2, 2016 Category: Drugs & Pharmacology Source Type: research

Antagonist Models for Relapse Prevention and Reducing HIV Risk
Abstract Naltrexone is an antagonist that binds tightly to μ-opioid receptors and blocks the subjective and analgesic effects of opioids. It does not produce physiologic dependence and precipitates withdrawal if administered to an opioid dependent person, thus starting it must begin with detoxification. It was first available in the mid-1970s as a 50 mg tablet that blocked opioids for 24–36 h if taken daily, or every 2–3 days at higher doses - for example: 100 mg Monday and Wednesday, 150 mg on Friday. From a pharmacological perspective it worked very well and was hoped to b...
Source: Journal of NeuroImmune Pharmacology - February 27, 2016 Category: Drugs & Pharmacology Source Type: research

Anti-Inflammatory and Antioxidant Mechanism of Tangeretin in Activated Microglia
In this study, we examined the anti-inflammatory effect of tangeretin in lipopolysaccharide (LPS)-stimulated microglia. We first observed that tangeretin inhibited LPS-induced production of nitric oxide, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β, as well as LPS-induced mRNA expression of inducible nitric oxide synthases and cytokines. Additionally, we found that the activities, mRNA levels, and protein levels of matrix metalloproteinase (MMP)-3 and MMP-8 were inhibited, while the expression of tissue inhibitor of metalloproteinase-2 was enhanced by tangeretin in LPS-stimulated microglia. Further mecha...
Source: Journal of NeuroImmune Pharmacology - February 22, 2016 Category: Drugs & Pharmacology Source Type: research

The Metabotropic Glutamate Receptor 4 Positive Allosteric Modulator ADX88178 Inhibits Inflammatory Responses in Primary Microglia
Abstract While the specific trigger of Parkinson Disease (PD) in most patients is unknown, considerable evidence suggests that the neuroinflammatory response makes an essential contribution to the neurodegenerative process. Drugs targeting metabotropic glutamate receptors (mGlu receptors), 7 Transmembrane (7TM) spanning/G protein coupled receptors that bind glutamate, are emerging as therapeutic targets for PD and may have anti-inflammatory properties. ADX88178 is novel potent, selective, and brain-penetrant positive allosteric modulator of the mGlu4 which is under evaluation for treatment of PD and other neurolog...
Source: Journal of NeuroImmune Pharmacology - February 12, 2016 Category: Drugs & Pharmacology Source Type: research

A Smartphone Application Supporting Recovery from Heroin Addiction: Perspectives of Patients and Providers in China, Taiwan, and the USA
Abstract Smartphone-based interventions are increasingly used to support self-monitoring, self-management, and treatment and medication compliance in order to improve overall functioning and well-being. In attempting to develop a smartphone application (S-Health) that assists heroin-dependent patients in recovery, a series of focus groups (72 patients, 22 providers) were conducted in China, Taiwan, and the USA to obtain their perspectives on its acceptance and potential adoption. Data were analyzed according to the Diffusion of Innovation (DOI) theory of characteristics important to the adoption of innovation. Imp...
Source: Journal of NeuroImmune Pharmacology - February 4, 2016 Category: Drugs & Pharmacology Source Type: research

Brain Invasion by CD4 + T Cells Infected with a Transmitted/Founder HIV-1 BJZS7 During Acute Stage in Humanized Mice
Abstract Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is one of the common causes of cognitive dysfunction and morbidity among infected patients. However, to date, it remains unknown if a transmitted/founder (T/F) HIV-1 leads to neurological disorders during acute phase of infection. Since it is impossible to answer this question in humans, we studied NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ mice (NSG) reconstituted with human PBMC (NSG-HuPBL), followed by the peritoneal challenge with the chronic HIV-1JR-FL and the T/F HIV-1BJZS7, respectively. By measuring viral load, P24 antigenemia and...
Source: Journal of NeuroImmune Pharmacology - February 2, 2016 Category: Drugs & Pharmacology Source Type: research

Mitoapocynin Treatment Protects Against Neuroinflammation and Dopaminergic Neurodegeneration in a Preclinical Animal Model of Parkinson’s Disease
Abstract Mitochondrial dysfunction, oxidative stress and neuroinflammation have been implicated as key mediators contributing to the progressive degeneration of dopaminergic neurons in Parkinson’s disease (PD). Currently, we lack a pharmacological agent that can intervene in all key pathological mechanisms, which would offer better neuroprotective efficacy than a compound that targets a single degenerative mechanism. Herein, we investigated whether mito-apocynin (Mito-Apo), a newly-synthesized and orally available derivative of apocynin that targets mitochondria, protects against oxidative damage, glial-medi...
Source: Journal of NeuroImmune Pharmacology - February 2, 2016 Category: Drugs & Pharmacology Source Type: research

Neuropsychological, Neurovirological and Neuroimmune Aspects of Abnormal GABAergic Transmission in HIV Infection
Abstract The prevalence of HIV-associated neurocognitive disorders (HAND) remains high in patients with effective suppression of virus replication by combination antiretroviral therapy (cART). Several neurotransmitter systems were reported to be abnormal in HIV-infected patients, including the inhibitory GABAergic system, which mediates fine-tuning of neuronal processing and plays an essential role in cognitive functioning. To elucidate the role of abnormal GABAergic transmission in HAND, the expression of GABAergic markers was measured in 449 human brain specimens from HIV-infected patients with and without HAND....
Source: Journal of NeuroImmune Pharmacology - January 30, 2016 Category: Drugs & Pharmacology Source Type: research

Meta-Analysis of the COMT Val158Met Polymorphism in Major Depressive Disorder: Effect of Ethnicity
Abstract The COMT (catechol-O-methyltransferase) Val158Met polymorphism (rs4680) is a potential susceptibility variant for major depressive disorder (MDD). Although many genetic studies have examined the association between MDD and this polymorphism, the results were inconclusive. In the present study, we conducted a series of meta-analyses of samples consisting of 2905 MDD cases and 2403 controls with the goal of determining whether this variant indeed has any effect on MDD. We revealed a significant association in the comparison of Val/Val + Val/Met vs. Met/Met (OR =1.180; 95 % CI = 1.01...
Source: Journal of NeuroImmune Pharmacology - January 23, 2016 Category: Drugs & Pharmacology Source Type: research

The Second Insubria Autumn School on Neuroimmune Pharmacology: Repurposing Established Drugs for Novel Indications
Abstract The Second Insubria Autumn School on Neuroimmune Pharmacology was held at the University of Insubria in Varese (Italy) in November 16th–20th 2015, under the auspices of the Society on NeuroImmune Pharmacology, the Italian Society of Pharmacology, and the Italian Association for Neuroimmunology. The School was dedicated to the repurposing of established drugs for novel indications, considering the enormous opportunities for drug repositioning provided by the prominent innovative and interdisciplinary approaches peculiar to neuroimmune pharmacology. More than 40 graduate students and postdoctoral fell...
Source: Journal of NeuroImmune Pharmacology - December 16, 2015 Category: Drugs & Pharmacology Source Type: research

Erratum to: Changes in the NMR Metabolic Profile of Live Human Neuron-Like SH-SY5Y Cells Exposed to Interferon-α2
(Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - December 10, 2015 Category: Drugs & Pharmacology Source Type: research

Erratum to: Association of Autophagy in the Cell Death Mediated by Dihydrotestosterone in Autoreactive T Cells Independent of Antigenic Stimulation
(Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - December 1, 2015 Category: Drugs & Pharmacology Source Type: research

Association of Autophagy in the Cell Death Mediated by Dihydrotestosterone in Autoreactive T Cells Independent of Antigenic Stimulation
Abstract Gender disparity is well documented in the mouse model of experimental autoimmune encephalomyelitis (EAE) induced with proteolipid protein (PLP) 139–151, in which female, but not male, SJL mice show a chronic relapsing-remitting paralysis. Furthermore, dihydrotestosterone (DHT) has been shown to ameliorate the severity of EAE, but the underlying mechanisms of its protective effects are unclear. Using major histocompatibility complex (MHC) class II dextramers for PLP 139-151, we tested the hypothesis that DHT selectively modulates the...
Source: Journal of NeuroImmune Pharmacology - November 28, 2015 Category: Drugs & Pharmacology Source Type: research

Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques
Abstract Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) ...
Source: Journal of NeuroImmune Pharmacology - November 25, 2015 Category: Drugs & Pharmacology Source Type: research

Evidence for Epigenetic Regulation of Pro-Inflammatory Cytokines, Interleukin-12 and Interferon Gamma, in Peripheral Blood Mononuclear Cells from PTSD Patients
Abstract While Post Traumatic Stress Disorder (PTSD) is associated with immune dysfunction, the underlying mechanisms remain unclear. Studies suggest a role for involvement of epigenetic mechanisms and microRNAs (miRNAs). Here, we examined genome-wide histone and DNA methylation in the peripheral blood mononuclear cells (PBMCs) in PTSD. We noted significant differences in histone H3 trimethylation at K4, K9, K27 and K36 sites in PTSD when compared to control. While overall DNA methylation level did not differ significantly between control and PTSD, the promoters of several individual genes (e.g., Interferon gamma ...
Source: Journal of NeuroImmune Pharmacology - November 20, 2015 Category: Drugs & Pharmacology Source Type: research

Safety and Clinical Outcomes of Rituximab Treatment in Patients with Multiple Sclerosis and Neuromyelitis Optica: Experience from a National Online Registry (GRAID)
Discussion Safety data of almost 50 patient years of treatment with rituximab show that rituximab is tolerated well in MS/NMO patients. Infections and infusion reactions are the most common adverse events. Our data may help the individual physician to balance efficacy of rituximab against the risk. • Data on rituximab in MS and NMO are provided for almost 50 patientyears • Rituximab was tolerated well • No unexpected side effects were seen • Almost 80 % of the patients benefited at least partially from treatment (Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - November 20, 2015 Category: Drugs & Pharmacology Source Type: research

HIV-1 gp120Bal down-Regulates Phosphorylated NMDA Receptor Subunit 1 in Cortical Neurons via Activation of Glutamate and Chemokine Receptors
Abstract HIV-1 envelope glycoprotein gp120 (gp120) is a major virulence protein implicated in the pathogenesis of HIV-associated neurocognitive disorders (HAND). Although gp120 has been suggested to cause synaptic and neuronal injuries by disrupting NMDA receptor (NMDAR) function, the underlying mechanism is unclear. Here, we show that gp120Bal down-regulates the phosphorylation of the NMDAR subunit1 NR1 (at Ser896 and Ser897), which is essential for NMDAR function. This effect of gp120Bal is blocked by specific antagonists of both NMDA and AMPA receptors, indicating a critical role of synaptic activation. Further...
Source: Journal of NeuroImmune Pharmacology - November 18, 2015 Category: Drugs & Pharmacology Source Type: research

Comparative Neuroregenerative Effects of C-Phycocyanin and IFN-Beta in a Model of Multiple Sclerosis in Mice
Abstract Multiple Sclerosis (MS) therapies approved so far are unable to effectively reverse the chronic phase of the disease or improve the remyelination process. Here our aim is to evaluate the effects of C-Phycocyanin (C-Pc), a biliprotein from Spirulina platensis with anti-oxidant, anti-inflammatory and cytoprotective properties, in a chronic model of experimental autoimmune encephalomyelitis (EAE) in mice. C-Pc (2, 4 or 8 mg/kg i.p.) or IFN-beta (2000 IU, s.c.) was administered daily once a day or every other day, respectively, starting at disease onset, which differ among EAE mice between 11 a...
Source: Journal of NeuroImmune Pharmacology - November 10, 2015 Category: Drugs & Pharmacology Source Type: research

Generation and Disease Model Relevance of a Manganese Enhanced Magnetic Resonance Imaging-Based NOD/scid-IL-2R γ c null Mouse Brain Atlas
Abstract Strain specific mouse brain magnetic resonance imaging (MRI) atlases provide coordinate space linked anatomical registration. This allows longitudinal quantitative analyses of neuroanatomical volumes and imaging metrics for assessing the role played by aging and disease to the central nervous system. As NOD/scid-IL-2Rγ c null (NSG) mice allow human cell transplantation to study human disease, these animals are used to assess brain morphology. Manganese enhanced MRI (MEMRI) improves contrasts amongst brain components and as such can greatly help iden...
Source: Journal of NeuroImmune Pharmacology - November 10, 2015 Category: Drugs & Pharmacology Source Type: research

Changes in the NMR Metabolic Profile of Live Human Neuron-Like SH-SY5Y Cells Exposed to Interferon-α2
Abstract Interferon (IFN)-α2 is an extensively therapeutically used pro-inflammatory cytokine. Though its efficacy in controlling viral replication and tumor cells proliferation, administration of IFN-α2 is often associated with the development of central side effects. Magnetic resonance spectroscopy studies have demonstrated that IFN-α2 administration affects brain metabolism, however the exact nature of this effect is not completely known. We hypothesized that IFN-α2 can affect metabolic activity of human neuron-like SH-SY5Y cells which possess many characteristics of neurons and represen...
Source: Journal of NeuroImmune Pharmacology - November 5, 2015 Category: Drugs & Pharmacology Source Type: research

Tau-Directed Immunotherapy: A Promising Strategy for Treating Alzheimer’s Disease and Other Tauopathies
We report, here, that the conformation-specific antibody MC-1 produces some degree of improvement to both cognition and pathology in rTg4510. Pathological improvements as measured by Gallyas staining for fully formed tangles and phosphorylated tau appeared 4 days after intracranial injection into the hippocampus. We also examined markers for microglial activation, which did not appear impacted from treatment. Behavioral effects were noted after continuous infusion of antibodies into the lateral ventricle for approximately 2 weeks. We examined basic motor skills, which were not impacted by treatment, but did note ...
Source: Journal of NeuroImmune Pharmacology - November 4, 2015 Category: Drugs & Pharmacology Source Type: research

A Perspective on Roles Played by Innate and Adaptive Immunity in the Pathobiology of Neurodegenerative Disorders
Abstract Aberrant innate and adaptive immune responses are neurodegenerative disease effectors. Disease is heralded by a generalized, but subtle immune activation orchestrated by the release of extracellular prion-like aggregated and oxidized or otherwise modified proteins. These are responsible for an inflammatory neurotoxic cascade. The perpetrators of such events include effector T cells and activated microglia. What ensues are Alzheimer’s and Parkinson’s disease, amyotrophic lateral sclerosis and stroke with changed frequencies of effector T cell and reduced numbers or function of regulatory lympho...
Source: Journal of NeuroImmune Pharmacology - October 31, 2015 Category: Drugs & Pharmacology Source Type: research

Adaptive Immunity in Neurodegenerative and Neuropsychological Disorders
Abstract Neurodegenerative and neuropsychological disorders are becoming a greater proportion of the global disease burden; however the pathogenic mechanisms by which these disorders originate and contribute to disease progression are not well-described. Increasing evidence supports neuroinflammation as a common underlying component associated with the neuropathological processes that effect disease progression. This collection of articles explores the role of adaptive immunity in autoimmunity, neurodegeneration, neurotrauma, and psychological disorders. The section emphasizes the interactions of T cells with inna...
Source: Journal of NeuroImmune Pharmacology - October 26, 2015 Category: Drugs & Pharmacology Source Type: research

TIPE2 Play a Negative Role in TLR4-Mediated Autoimmune T Helper 17 Cell Responses in Patients with Myasthenia Gravis
Abstract Th17-related cytokines have been suggested to play a crucial role in myasthenia gravis (MG) pathogenesis.The tumor necrosis factor (TNF)-α-induced protein 8-like-2 (TNFAIP8L2 or TIPE2), is a newly identified member of the tumor necrosis TNFAIP8 family which is an essential negative regulator of both innate and adaptive immunity. In the present study, the expression of TIPE2 mRNA and protein in peripheral blood mononuclear cells (PBMC) from healthy and MG subjects were detected by Real-time PCR and Western blotting.The serum IL-6, IL-17 and IL-21 levels were tested by ELISA. Furthermore, PBMC from MG...
Source: Journal of NeuroImmune Pharmacology - October 24, 2015 Category: Drugs & Pharmacology Source Type: research

Novelty Seeking and Drug Addiction in Humans and Animals: From Behavior to Molecules
Abstract Global treatment of drug addiction costs society billions of dollars annually, but current psychopharmacological therapies have not been successful at desired rates. The increasing number of individuals suffering from substance abuse has turned attention to what makes some people more vulnerable to drug addiction than others. One personality trait that stands out as a contributing factor is novelty seeking. Novelty seeking, affected by both genetic and environmental factors, is defined as the tendency to desire novel stimuli and environments. It can be measured in humans through questionnaires and in rode...
Source: Journal of NeuroImmune Pharmacology - October 19, 2015 Category: Drugs & Pharmacology Source Type: research

Medial Septal NMDA Glutamate Receptors are Involved in Modulation of Blood Natural Killer Cell Activity in Rats
Abstract The purpose of the present study was to determine the specific role of the medial septal (MS) NMDA glutamate receptors on peripheral blood natural killer cell cytotoxicity (NKCC) and their (large granular lymphocyte, LGL) number, as well as the plasma concentration of tumor necrosis factor α (TNF-α) and corticosterone in male Wistar rats exposed to elevated plus maze (EPM) stress or non-stress conditions. The NMDA groups were injected with NMDA glutamate receptor agonist (N-methyl-D-aspartate; 0.25 μg/rat), the D-AP7 group was injected with DL-2-amino-7-phosphoheptanoate (0.1 μ...
Source: Journal of NeuroImmune Pharmacology - October 10, 2015 Category: Drugs & Pharmacology Source Type: research

Effect of HAART on Brain Organization and Function in HIV-Negative Subjects
Abstract HIV causes neural dysfunction in infected individuals. This dysfunction often manifests as cognitive symptoms and can be detected using neuroimaging. Highly active anti-retroviral therapy (HAART), in addition to providing virologic control, has reduced the number of profoundly impaired individuals but more mild forms of neurocognitive disorders remains prevalent. A potential confound in previous studies of HIV-associated cognitive dysfunction is that HAART may be neurotoxic. Thus, observed effects, attributed to HIV, may be in part due to HAART. It is unclear whether and to what extent current medications...
Source: Journal of NeuroImmune Pharmacology - October 7, 2015 Category: Drugs & Pharmacology Source Type: research

Opposing Effects of NGF and proNGF on HIV Induced Macrophage Activation
In this study we evaluated the interactions between neurotrophins and HIV induced macrophage activation. HIV stimulation of macrophages induced a neurotoxic phenotype characterized by the expression of podosomes, suppression of calcium spiking and increased neurotoxin production. The secretome of the activated macrophages revealed a bias toward anti-angiogenic like activity and increased secretion of MMP-9. Co-stimulation with NGF and HIV suppressed neurotoxin secretion, increased calcium spiking, suppressed podosome expression and reversed 86 % of the proteins secreted in response to HIV, including MMP-9 and many gro...
Source: Journal of NeuroImmune Pharmacology - September 29, 2015 Category: Drugs & Pharmacology Source Type: research

Association of Autophagy in the Cell Death Mediated by Dihydrotestosterone in Autoreactive T Cells Independent of Antigenic Stimulation
Abstract Gender disparity is well documented in the mouse model of experimental autoimmune encephalomyelitis (EAE) induced with proteolipid protein (PLP) 139–151, in which female, but not male, SJL mice show a chronic relapsing-remitting paralysis. Furthermore, dihydrotestosterone (DHT) has been shown to ameliorate the severity of EAE, but the underlying mechanisms of its protective effects are unclear. Using major histocompatibility complex (MHC) class II dextramers for PLP 139-151, we tested the hypothesis that DHT selectively modulates the expansion and functionalities of antigen-specific T cells. Unexpec...
Source: Journal of NeuroImmune Pharmacology - September 29, 2015 Category: Drugs & Pharmacology Source Type: research

Targeted Stage-Specific Inflammatory microRNA Profiling in Urine During Disease Progression in Experimental Autoimmune Encephalomyelitis: Markers of Disease Progression and Drug Response
Abstract Recently, microRNAs (miRNAs) have been implicated in regulating neuroinflammatory and demyelinative responses in multiple sclerosis (MS) and its mouse model of experimental autoimmune encephalomyelitis (EAE). miRNAs have also been studied as biomarkers of disease pathology and drug-response in MS. However, no complete miRNA profiling at various stages of EAE disease has been examined, especially in the urine. We carried out a systematic analysis of miRNAs in the urine exosomes as well as in the plasma and spinal cord at pre-onset, onset and peak stages of EAE established in the chronic B6 mice model. For ...
Source: Journal of NeuroImmune Pharmacology - August 15, 2015 Category: Drugs & Pharmacology Source Type: research

Validation of Flow Cytometry and Magnetic Bead-Based Methods to Enrich CNS Single Cell Suspensions for Quiescent Microglia
We describe and validate an inexpensive and simple approach to obtain enriched single cell suspensions of quiescent parenchymal and perivascular microglia from the mouse cerebellum and hypothalamus. Following preparation of regional CNS single cell suspensions, we remove myelin debris, and then perform two serial enrichment steps for cells expressing surface CD11b. Myelin depletion and CD11b enrichment are both accomplished using antigen-specific magnetic beads in an automated cell separation system. Flow cytometry of the resultant suspensions shows a significant enrichment for CD11b(+)/CD45(+) cells (perivascular microgli...
Source: Journal of NeuroImmune Pharmacology - August 11, 2015 Category: Drugs & Pharmacology Source Type: research