In a Model of Neuroinflammation Designed to Mimic Delirium, Quetiapine Reduces Cortisol Secretion and Preserves Reversal Learning in the Attentional Set Shifting Task
AbstractQuetiapine, an atypical antipsychotic medication has lacked pre-clinical validation for its purported benefits in the treatment of delirium. This laboratory investigation examined the effects of quetiapine on the attentional set shifting task (ASST), a measure of cognitive flexibility and executive functioning, in a rodent model of lipopolysaccharide (LPS) mediated neuroinflammation. 19 Sprague Dawley female rats were randomly selected to receive intraperitoneal placebo (N = 5), LPS and placebo (N = 7) or LPS and quetiapine (n = 7) and performed the ASST. We measured trials...
Source: Journal of NeuroImmune Pharmacology - May 22, 2019 Category: Drugs & Pharmacology Source Type: research

Where Is Dopamine and how do Immune Cells See it?: Dopamine-Mediated Immune Cell Function in Health and Disease
AbstractDopamine is well recognized as a neurotransmitter in the brain, and regulates critical functions in a variety of peripheral systems. Growing research has also shown that dopamine acts as an important regulator of immune function. Many immune cells express dopamine receptors and other dopamine related proteins, enabling them to actively respond to dopamine and suggesting that dopaminergic immunoregulation is an important part of proper immune function. A detailed understanding of the physiological concentrations of dopamine in specific regions of the human body, particularly in peripheral systems, is critical to the...
Source: Journal of NeuroImmune Pharmacology - May 11, 2019 Category: Drugs & Pharmacology Source Type: research

Proteomic Profiling of Exosomes Derived from Plasma of HIV-Infected Alcohol Drinkers and Cigarette Smokers
This study presents a proteomic analysis of plasma-derived exosomes from HIV-infected alcohol drinkers and smokers. Among the proteins altered due to drug-abuse, hemopexin and properdin were of highest significance. These proteins can be potential biomarkers for co-morbid conditions associated with drug abuse in HIV-patients. (Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

FTY720 Inhibits MPP + -Induced Microglial Activation by Affecting NLRP3 Inflammasome Activation
In conclusion, FTY720 may reduce PD progression by inhibiting NLRP3 inflammasome activation via its effects on ROS generation and p65 activation in microglia. These findings provide novel insights into the mechanisms underlying the therapeutic effects of FTY720, suggesting its potential as a novel therapeutic strategy against PD.Graphical AbstractFTY720 may reduce ROS production by inhibiting the PI3K/AKT/GSK-3 β signaling pathway, while at the same time reducing p65 phosphorylation, thus decreasing NLRP3 inflammasome activation through these two pathways, ultimately reducing microglia activation-induced neuronal dama...
Source: Journal of NeuroImmune Pharmacology - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

Toll-Like Receptor 4 Promotes Th17 Lymphocyte Infiltration Via CCL25/CCR9 in Pathogenesis of Experimental Autoimmune Encephalomyelitis
AbstractToll-like receptor 4 (TLR4) is a key component in innate immunity and has been linked to central nervous system (CNS) inflammation diseases, such as multiple sclerosis (MS), an inflammatory disorder induced by autoreactive Th17 cells. In our study, we found that TLR4 deficient (TLR4−/−) mice were inadequate to induce experimental autoimmune encephalomyelitis (EAE), characterized by low clinic score and weight loss, alleviative demyelinating, as well as decreased inflammatory cell infiltration in the spinal cord. In the lesion area of EAE mice, loss of TLR4 down-regulated the secretion of inflammatory cy...
Source: Journal of NeuroImmune Pharmacology - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

Dopaminergic Agents in Rheumatoid Arthritis
AbstractClinical evidences suggest a causal relationship between rheumatoid arthritis (RA) and the dopaminergic system, and several studies described an alteration of the disease in patients treated with dopaminergic agents. Despite these interesting results, potential direct effects of dopamine on RA have not been intensively considered until the last decade. Recent studies confirm a direct effect of dopamine on the systemic immune response as well as on bone remodeling and on joint inflammation, both in humans and in different animal models of arthritis. While more research is necessary to accurately determine the effect...
Source: Journal of NeuroImmune Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Dopaminergic Therapeutics in Multiple Sclerosis: Focus on Th17-Cell Functions
AbstractMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with an autoimmune mechanism of development. Currently, one of the most promising directions in the study of MS pathogenesis are the neuroimmune interactions. Dopamine is one of the key neurotransmitters in CNS. Furthermore, dopamine is a direct mediator of interactions between the immune and nervous systems and can influence MS pathogenesis by modulating immune cells activity and cytokine production. Recent studies have shown that dopamine can enhance or inhibit the functions of innate and adaptive immune sy...
Source: Journal of NeuroImmune Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Next Generation Precision Medicine: CRISPR-mediated Genome Editing for the Treatment of Neurodegenerative Disorders
AbstractDespite significant advancements in the field of molecular neurobiology especially neuroinflammation and neurodegeneration, the highly complex molecular mechanisms underlying neurodegenerative diseases remain elusive. As a result, the development of the next generation neurotherapeutics has experienced a considerable lag phase. Recent advancements in the field of genome editing offer a new template for dissecting the precise molecular pathways underlying the complex neurodegenerative disorders. We believe that the innovative genome and transcriptome editing strategies offer an excellent opportunity to decipher nove...
Source: Journal of NeuroImmune Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Extracellular Vesicles: Intercellular Mediators in Alcohol-Induced Pathologies
AbstractThough alcoholic liver injury plays the primary role in direct alcohol-related morbidity, alcohol consumption is also interlinked with many other diseases in extra-hepatic tissues/organs. The mechanism of alcoholic tissue injury is well documented, however the mechanisms that affect extra-hepatic tissues have not yet been well defined. Extracellular vesicles (EVs) such as exosomes and microvesicles, have been identified as key components of alcohol-induced extra-hepatic effects. We have reviewed the recent findings on the potential impact of alcohol-modified EVs/exosomes production and their downstream effects on e...
Source: Journal of NeuroImmune Pharmacology - April 6, 2019 Category: Drugs & Pharmacology Source Type: research

Resveratrol (3, 5, 4 ′-Trihydroxy- trans- Stilbene) Attenuates a Mouse Model of Multiple Sclerosis by Altering the miR-124/Sphingosine Kinase 1 Axis in Encephalitogenic T Cells in the Brain
AbstractResveratrol (3,5,4 ′-trihydroxy-trans-stilbene) (RES) is a naturally-derived phytoestrogen found in the skins of red grapes and berries and has potential as a novel and effective therapeutic agent. In the current study, we investigated the role of microRNA (miRNA) in RES-mediated attenuation of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. Administration of RES effectively decreased disease severity, including inflammation and central nervous system immune cell infiltration. miRNA microarray analysis revealed an altered miRNA profile in encephalitogenic CD4+ T cells fr...
Source: Journal of NeuroImmune Pharmacology - April 2, 2019 Category: Drugs & Pharmacology Source Type: research

The 25th Scientific Conference of the Society on Neuroimmune Pharmacology: Program and Abstracts
(Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - March 25, 2019 Category: Drugs & Pharmacology Source Type: research

Chronic Intrahippocampal Infusion of HIV-1 Neurotoxic Proteins: A Novel Mouse Model of HIV-1 Associated Inflammation and Neural Stem Cell Dysfunction
AbstractHIV-1 infection causes chronic neuroinflammation resulting in cognitive decline associated with diminution of survival of neural stem cells (NSC). In part, this is attributable to production of toxic viral proteins (gp120 and tat) by infected cells in the brain that can activate microglia. Here, we evaluated a novel model for HIV-1 neuropathogenesis by direct administration of viral proteins into the hippocampus. Chronic administration of either HIV-1 gp120 or tat over 14  days significantly decreased NSC proliferation, survival and neuroblast formation (by 32–37%) within the hippocampal subgranular zone...
Source: Journal of NeuroImmune Pharmacology - March 23, 2019 Category: Drugs & Pharmacology Source Type: research

Utilization of the CRISPR-Cas9 Gene Editing System to Dissect Neuroinflammatory and Neuropharmacological Mechanisms in Parkinson ’s Disease
AbstractChronic and debilitating neurodegenerative diseases, such as Parkinson ’s disease (PD), impose an immense medical, emotional, and economic burden on patients and society. Due to a complex interaction between genetic and environmental risk factors, the etiology of PD remains elusive. However, the cumulative evidence emerging from clinical and experimental research ove r the last several decades has identified mitochondrial dysfunction, oxidative stress, neuroinflammation, and dysregulated protein degradation as the main drivers of PD neurodegeneration. The genome-editing system CRISPR (clustered regularly inte...
Source: Journal of NeuroImmune Pharmacology - March 16, 2019 Category: Drugs & Pharmacology Source Type: research

CRISPR/Cas9 Editing of Glia Maturation Factor Regulates Mitochondrial Dynamics by Attenuation of the NRF2/HO-1 Dependent Ferritin Activation in Glial Cells
In this study, we examined the effect of GMF editing by using the CRISPR/Cas9 technique in BV2 microglial cells (hereafter referred to as BV2-G) on oxidative stress and nuclear factor erythroid 2-related factor 2 (NRF2)/Hemeoxygenase1 (HO-1)-dependent ferritin activation after treatment with (1- methyl-4-phenylpyridinium) MPP+. Knockout of GMF in BV2-G cells significantly attenuated oxidative stress via reduced ROS production and calcium flux. Furthermore, deficiency of GMF significantly reduced nuclear translocation of NRF2, which modulates HO-1 and ferritin activation, cyclooxygenase 2 (COX2) and nitric oxide syntha...
Source: Journal of NeuroImmune Pharmacology - February 27, 2019 Category: Drugs & Pharmacology Source Type: research

Can Our Guts Tell Us Anything About MS?
(Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - February 15, 2019 Category: Drugs & Pharmacology Source Type: research

Adrenergic Modulation of Hematopoiesis
AbstractHematopoiesis produce every day billions of blood cells and takes place in the bone marrow (BM) by the proliferation and differentiation of hematopoietic stem cells (HSC). HSC are found mainly adjacent to the BM vascular sinusoids where endothelial cells and mesenchimal stromal cells promote HSC maintenance by producing a variety of factors. Other cell types that regulate HSC niches include sympathetic nerves, non –myelinating Schwann cells and a variety of mature hematopoietic cells such as macrophages, neutrophils, and megakaryocytes. This review will focus on the role of adrenergic signals, i.e. of catecho...
Source: Journal of NeuroImmune Pharmacology - February 14, 2019 Category: Drugs & Pharmacology Source Type: research

Inhibition of Bruton ’s Tyrosine Kinase Modulates Microglial Phagocytosis: Therapeutic Implications for Alzheimer’s Disease
AbstractBruton ’s tyrosine kinase (BTK), a critical component of B cell receptor signaling, has recently been implicated in regulation of the peripheral innate immune response. However, the role of BTK in microglia, the resident innate immune cells of the central nervous system, and its involvement in the pathob iology of neurodegenerative disease has not been explored. Here we found that BTK is a key regulator of microglial phagocytosis. Using potent BTK inhibitors and small interfering RNA (siRNA) against BTK, we observed that blockade of BTK activity decreased activation of phospholipase gamma 2, a recen tly ident...
Source: Journal of NeuroImmune Pharmacology - February 13, 2019 Category: Drugs & Pharmacology Source Type: research

Dissociable Contributions of Precuneus and Cerebellum to Subjective and Objective Neuropathy in HIV
This study was conducted in 109 healthy controls and 57 HIV-infected individuals to investigate CNS regions associated with neuropathy. An index of objective neuropathy was computed based on 4 measures: deep tendon ankle reflex, vibration sense (great toes), position sense (great toes), and 2-point discrimination (feet). Subjective neuropathy (self-report of pain, aching, or burning; pins and needles; or numbness in legs or feet) was also evaluated. Structural MRI data were available for 126/166 cases. The HIV relative to the healthy control group was impaired on all 4 signs of neuropathy. Within the HIV group, an objectiv...
Source: Journal of NeuroImmune Pharmacology - February 11, 2019 Category: Drugs & Pharmacology Source Type: research

Editor ’s Commentary for Special Issue: “The Role of Macrophages in HIV Persistence”
AbstractMacrophages as reservoirs for persistent HIV infection has gained renewed importance, with an intense research focus dedicated to eradication strategies. Clearance of both latent and productive HIV from these important reservoirs is essential for successful eradication. This spe cial theme issue contains 11 papers, including 6 Invited Reviews, 1 Brief Report and 4 Original Articles, that focus on the various aspects of the macrophage as pertains to HIV persistence, latency and cure. These topics include: functional latency of macrophages and microglia, the link between peripheral monocytes and pathogenesis, macroph...
Source: Journal of NeuroImmune Pharmacology - February 9, 2019 Category: Drugs & Pharmacology Source Type: research

In Appreciation for a Job Well Done!
(Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - February 8, 2019 Category: Drugs & Pharmacology Source Type: research

Ultrasensitive Detection of Aggregated α-Synuclein in Glial Cells, Human Cerebrospinal Fluid, and Brain Tissue Using the RT-QuIC Assay: New High-Throughput Neuroimmune Biomarker Assay for Parkinsonian Disorders
AbstractAdult-onset neurodegenerative disorders, like Parkinson ’s disease (PD) and dementia with Lewy bodies (DLB), that share the accumulation of aggregated α-synuclein (αSynagg) as their hallmark molecular pathology are collectively known as α-synucleinopathies. Diagnosing α-synucleinopathies requires the post-mortem detection of αSynagg in various brain regions. Recent efforts to measure αSynagg in living patients include quantifying αSynagg in different biofluids as a biomarker for PD. We adopted the real-time quaking-induced conversion (RT-QuIC) assay to detect very low...
Source: Journal of NeuroImmune Pharmacology - January 31, 2019 Category: Drugs & Pharmacology Source Type: research

Targeting the Dopaminergic System in Autoimmunity
AbstractDopamine has emerged as a fundamental regulator of inflammation. In this regard, it has been shown that dopaminergic signalling pathways are key players promoting homeostasis between the central nervous system and the immune system. Dysregulation in the dopaminergic system affects both innate and adaptive immunity, contributing to the development of numerous autoimmune and inflammatory pathologies. This makes dopamine receptors interesting therapeutic targets for either the development of new treatments or repurposing of already available pharmacological drugs. Dopamine receptors are broadly expressed on different ...
Source: Journal of NeuroImmune Pharmacology - January 19, 2019 Category: Drugs & Pharmacology Source Type: research

Monocyte and Lymphocyte Activation and Regulation in Multiple Sclerosis Patients. Therapy Effects
AbstractAnalysis of gut barrier status, monocyte and lymphocyte activation and T regulatory (Treg) cells at diagnosis before and after therapy, in patients with multiple sclerosis (MS). Analysis of differential effects of interferon beta (IFN- β), glatiramer acetate (GA) and natalizumab. Thirty-five patients with untreated MS were included. Gut barrier status (serum concentrations of intestinal fatty acid binding protein), monocyte (serum levels of soluble CD14, soluble CD163 and interleukin 6) and T lymphocyte activation (CD4 + DR+ and CD8 + DR+) and Treg (CD4 + CD25highFoxP3...
Source: Journal of NeuroImmune Pharmacology - January 16, 2019 Category: Drugs & Pharmacology Source Type: research

Protective Effects of 1-Methylnicotinamide on A β 1–42 -Induced Cognitive Deficits, Neuroinflammation and Apoptosis in Mice
AbstractThe neurotoxicity of A β peptides has been well documented, but effective neuroprotective approaches against Aβ neurotoxicity are unavailable. In the present study, we investigated effects of 1-Methylnicotinamide (MNA), known as a main metabolite of nicotinamide (NA), on the impairment of learning and memory induced by Aβ and the underlying mechanisms. We found that intragastric administration of MNA at 100 or 200 mg/kg for 3 weeks significantly reversed bilateral intrahippocampal injection of Aβ1 –42-induced cognitive impairments in the Morris water maze (MWM), Y-maze and Novel ...
Source: Journal of NeuroImmune Pharmacology - January 11, 2019 Category: Drugs & Pharmacology Source Type: research

Broad Spectrum Mixed Lineage Kinase Type 3 Inhibition and HIV-1 Persistence in Macrophages
AbstractMixed lineage kinases (MLKs) are a group of serine-threonine kinases that evolved in part to respond to endogenous and exogenous insults that result in oxidative stress and pro-inflammatory responses from innate immune cells. Human immunodeficiency virus type 1 (HIV-1) thrives in these conditions and is associated with the development of associated neurocognitive disorders (HAND). As part of a drug discovery program to identify new therapeutic strategies for HAND, we created a library of broad spectrum MLK inhibitors with drug-like properties. Serendipitously, the lead compound, URMC-099 has proved useful not only ...
Source: Journal of NeuroImmune Pharmacology - January 7, 2019 Category: Drugs & Pharmacology Source Type: research

Beta2-Adrenoceptor Agonists in Parkinson ’s Disease and Other Synucleinopathies
AbstractEvidence supporting the use of β2AR agonists in synucleinopathies is rapidly growing. Findings come from different scientific approaches. Molecular and immunological data suggest that adrenergic stimulation may decrease both α-synuclein (α-syn) deposition and pro-inflammatory/neurotoxic molecules release. Small open label clin ical trials including a total number of 25 Parkinson’s disease (PD) patients, in which the β2AR agonist salbutamol was added to levodopa, suggest a promising symptomatic benefit. In line with these findings, epidemiological studies investigating the risk of PD deve...
Source: Journal of NeuroImmune Pharmacology - January 7, 2019 Category: Drugs & Pharmacology Source Type: research

Letter to Editor
(Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - December 12, 2018 Category: Drugs & Pharmacology Source Type: research

Role of Macrophage Dopamine Receptors in Mediating Cytokine Production: Implications for Neuroinflammation in the Context of HIV-Associated Neurocognitive Disorders
AbstractDespite the success of combination anti-retroviral therapy (cART), around 50% of HIV-infected individuals still display a variety of neuropathological and neurocognitive sequelae known as NeuroHIV. Current research suggests these effects are mediated by long-term changes in CNS function in response to chronic infection and inflammation, and not solely due to active viral replication. In the post-cART era, drug abuse is a major risk-factor for the development of NeuroHIV, and increases extracellular dopamine in the CNS. Our lab has previously shown that dopamine can increase HIV infection of primary human macrophage...
Source: Journal of NeuroImmune Pharmacology - December 5, 2018 Category: Drugs & Pharmacology Source Type: research

Molecular Imaging of Neuroinflammation in HIV
AbstractThe development of combined antiretroviral therapy (cART) has increased the lifespan of persons living with HIV (PLWH), with most PLWH having a normal life expectancy. While significant progress has occurred, PLWH continue to have multiple health complications, including HIV associated neurocognitive disorders (HAND). While the exact cause of HAND is not known, persistent neuroinflammation is hypothesized to be an important potential contributor. Molecular imaging using positron emission tomography (PET) can non-invasively evaluate neuroinflammation. PET radiotracers specific for increased expression of the translo...
Source: Journal of NeuroImmune Pharmacology - December 5, 2018 Category: Drugs & Pharmacology Source Type: research

Reply to Letter to the Editor
(Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - December 1, 2018 Category: Drugs & Pharmacology Source Type: research

CNS-Wide over Expression of Fractalkine Improves Cognitive Functioning in a Tauopathy Model
AbstractAccumulating evidence increasingly implicates regulation of neuroinflammation as a potential therapeutic target in Alzheimer ’s disease and other neurodegenerative disorders. Fractalkine (FKN) is a unique chemokine that is expressed and secreted by neurons and reduces expression of pro-inflammatory genes. To further demonstrate the utility of agents that increase FKN signaling throughout the central nervous system as possible therapies for AD, we assessed the impact of soluble FKN (sFKN) over expression on cognition in tau depositing rTg450 mice after the onset of cognitive deficits. Using adeno-associated vi...
Source: Journal of NeuroImmune Pharmacology - November 29, 2018 Category: Drugs & Pharmacology Source Type: research

Osteopontin Attenuates Secondary Neurodegeneration in the Thalamus after Experimental Stroke
AbstractCortical cerebral ischemia elicits neuroinflammation as well as secondary neuronal degeneration in remote areas. Locally distinct and specific secondary neurodegeneration affecting thalamic nuclei connected to cortical areas highlights such processes. Osteopontin (OPN) is a cytokine-like glycoprotein that is excreted in high amounts after cerebral ischemia and exerts various immunomodulatory functions. We here examined putative protective effects of OPN in secondary thalamic degeneration. We subjected male Wistar rats to photothrombosis and subsequently injected OPN or placebo intracerebroventricularly. Immunohisto...
Source: Journal of NeuroImmune Pharmacology - November 28, 2018 Category: Drugs & Pharmacology Source Type: research

Melatonin Rescue Oxidative Stress-Mediated Neuroinflammation/ Neurodegeneration and Memory Impairment in Scopolamine-Induced Amnesia Mice Model
AbstractCognitive decline and memory impairment induced by oxidative brain damage are the critical pathological hallmarks of Alzheimer ’s disease (AD). Based on the potential neuroprotective effects of melatonin, we here explored the possible underlying mechanisms of the protective effect of melatonin against scopolamine-induced oxidative stress-mediated c-Jun N-terminal kinase (JNK) activation, which ultimately results in synapt ic dysfunction, neuroinflammation, and neurodegeneration. According to our findings, scopolamine administration resulted in LPO and ROS generation and decreased the protein levels of antioxi...
Source: Journal of NeuroImmune Pharmacology - November 27, 2018 Category: Drugs & Pharmacology Source Type: research

Mechanisms of Blood-Brain Barrier Disruption in Herpes Simplex Encephalitis
AbstractHerpes simplex encephalitis (HSE) is often caused by infection with herpes simplex virus 1 (HSV-1), a neurotropic double-stranded DNA virus. HSE infection always impacts the temporal and frontal lobes or limbic system, leading to edema, hemorrhage, and necrotic changes in the brain parenchyma. Additionally, patients often exhibit severe complications following antiviral treatment, including dementia and epilepsy. HSE is further associated with disruptions to the blood-brain barrier (BBB), which consists of microvascular endothelial cells, tight junctions, astrocytes, pericytes, and basement membranes. Following an ...
Source: Journal of NeuroImmune Pharmacology - November 19, 2018 Category: Drugs & Pharmacology Source Type: research

Editors ’ Commentary for Special Issue: The 2017 CALDAR Summer Institute and International Conference Promoting Global Health—Precision Research in Substance Abuse, HIV, and Care
AbstractThis special issue contains 11 papers, including 3 Invited Reviews, one Brief Report and 6 Original Articles, which highlight the work by selected presenters at the third meeting of the biennial Conference Series to Promote Global Health held on August 15 –17, 2017 in Los Angeles University City, California, USA. The Conference Series is sponsored by the National Institute on Drug Abuse, of the U.S. National Institutes of Health. A major goal of the conference is to promote international collaboration that will improve practices in the US and other countries, which is greatly needed to keep the scientific, tr...
Source: Journal of NeuroImmune Pharmacology - October 31, 2018 Category: Drugs & Pharmacology Source Type: research

AAV-Vectored Fms-Related Tyrosine Kinase 3 Ligand Inhibits CD34 + Progenitor Cell Engraftment in Humanized Mice
AbstractHumanized mice have become useful animal models for HIV/AIDS. Since NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ (NSG) mice allow the engraftment of primary human immune cells, we aim to determine the role of human Fms-related tyrosine kinase 3 ligand (hFlt3L), a major growth factor for dendritic cells (DCs), in regulating the differentiation of cord blood-derived CD34+ progenitor cells in this murine species. Soluble recombinant hFlt3L protein and AAV-vectored hFlt3L were administrated before or after human CD34+ progenitor cell transplantation, respectively. We then measured the peripheral levels of hFlt3L by ELISA. Meantim...
Source: Journal of NeuroImmune Pharmacology - October 30, 2018 Category: Drugs & Pharmacology Source Type: research

Most Current Smokers Desire Genetic Susceptibility Testing and Genetically-Efficacious Medication
This study determines (1) which current smokers are receptive to genetic susceptibility testing for nicotine dependence and (2) to what potential extent smokers motivated to quit desire to take smoking cessation medication when hypothetical genetic results predict their pharmacogenetic medication response. Current smokers from a genetic nicotine dependence study (n = 1306) and an ongoing smoking cessation trial (n = 209) were surveyed on their hypothetical interest in seeing genetic testing results related to risk of nicotine dependence. Most current smokers (84.8%) reported high interest in rec...
Source: Journal of NeuroImmune Pharmacology - October 29, 2018 Category: Drugs & Pharmacology Source Type: research

P2X7 Receptor Antagonist A804598 Inhibits Inflammation in Brain and Liver in C57BL/6J Mice Exposed to Chronic Ethanol and High Fat Diet
AbstractChronic low-grade neuroinflammation is increasingly implicated in organ damage caused by alcohol abuse. Purinergic P2X7 receptors (P2X7Rs) play an important role in the generation of inflammatory responses during a number of CNS pathologies as evidenced from studies using pharmacological inhibition approach. P2X7Rs antagonism has not been tested during chronic alcohol abuse. In the present study, we tested the potential of P2X7R antagonist A804598 to reduce/abolish alcohol-induced neuroinflammation using chronic intragastric ethanol infusion and high-fat diet (Hybrid) in C57BL/6J mice. We have previously demonstrat...
Source: Journal of NeuroImmune Pharmacology - October 23, 2018 Category: Drugs & Pharmacology Source Type: research

Age-Induced Spatial Memory Deficits in Rats Are Correlated with Specific Brain Region Alterations in Microglial Morphology and Gene Expression
AbstractEffect of age and ladostigil treatment (1  mg/kg/day), given for 6 months to 16 month old rats, was investigated on microglial morphology in brain regions associated with control of spatial learning. This was assessed in the Morris water maze (MWM). Microglial morphology was assessed with diaminobenzidine and fluorescent staining with Ib a1 and CD11b in these brain regions. Aging did not change the number of microglia in the parietal cortex (PC) or hippocampal CA1 region (CA1-HC), but decreased microglial process tips in the CA1-HC, increased the area fraction stained by CD11b and number of bulbs on ...
Source: Journal of NeuroImmune Pharmacology - October 20, 2018 Category: Drugs & Pharmacology Source Type: research

Current and Future Therapeutic Strategies for Lentiviral Eradication from Macrophage Reservoirs
AbstractMacrophages, one of the most abundant populations of leukocytes in the body, function as the first line of defense against pathogen invaders. Human Immunodeficiency virus 1 (HIV-1) remains to date one of the most extensively studied viral infections. Naturally occurring lentiviruses in domestic and primate species serve as valuable models to investigate lentiviral pathogenesis and novel therapeutics. Better understanding of the role macrophages play in HIV pathogenesis will aid in the advancement towards a cure. Even with current efficacy of first- and second-line Antiretroviral Therapy (ART) guidelines and future ...
Source: Journal of NeuroImmune Pharmacology - October 13, 2018 Category: Drugs & Pharmacology Source Type: research

Urinary and Plasma Metabolomics Identify the Distinct Metabolic Profile of Disease State in Chronic Mouse Model of Multiple Sclerosis
AbstractIdentification of non-invasive biomarkers of disease progression in multiple sclerosis (MS) is critically needed for monitoring the disease progression and for effective therapeutic interventions. Urine is an attractive source for non-invasive biomarkers because it is easily obtained in the clinic. In search of a urine metabolite signature of progression in chronic experimental autoimmune encephalomyelitis (EAE), we profiled urine at the chronic stage of the disease (day 45 post immunization) by global untargeted metabolomics. Using a combination of high-throughput liquid-and-gas chromatography with mass spectromet...
Source: Journal of NeuroImmune Pharmacology - October 12, 2018 Category: Drugs & Pharmacology Source Type: research

Sigma-1 Receptor Antagonist (BD1047) Decreases Cathepsin B Secretion in HIV-Infected Macrophages Exposed to Cocaine
AbstractPathogenesis of HIV-associated neurocognitive disorders (HAND) is mediated through the infiltration of perivascular macrophages into the brain with the secretion of viral, neurotoxic and inflammatory proteins. One of these proteins is cathepsin B (CATB), a lysosomal cysteine protease that induces neuronal apoptosis, and increases in plasma and cerebrospinal fluid from HIV-1 infected patients (Cantres-Rosario et al. AIDS 27(3):347 –356,2013). Cocaine further potentiates CATB neurotoxicity in vitro and in vivo (Zen ón et al. J NeuroImmune Pharmacol 9(5):703–715,2014). Modulation of sigma-1 (Sig1R) ...
Source: Journal of NeuroImmune Pharmacology - October 10, 2018 Category: Drugs & Pharmacology Source Type: research

Reduction in Cannabis Use and Functional Status in Physical Health, Mental Health, and Cognition
This study explores if reduction in cannabis use to a lower level of use is related to improved physical health, mental health, and perceived cognitive functions. Study participants with a history of problematic cannabis use (n = 111) completed assessments. Regression models were used to explore the relationship between past 30-day cannabis use levels (abstinent [57%], low use [22%] defined as less than or equal to 3 days per week, and heavy use [22%] defined as 4 or more days of use per week) and functional status i n physical health, mental health, and cognition. Compared to heavy users, both abstinent...
Source: Journal of NeuroImmune Pharmacology - October 3, 2018 Category: Drugs & Pharmacology Source Type: research

Prediction of Schizophrenia Diagnosis by Integration of Genetically Correlated Conditions and Traits
In this study, we explored polygenic scores (PGSs) from genetically related conditions and traits to predict schizophrenia diagnosis using both logistic regression and deep neural network (DNN) models. We used the combined Molecular Genetics of Schizophrenia and Swedish Schizophrenia Case Control Study (MGS  + SSCCS) data for training and testing the models, and used the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) data as independent validation. We screened 28 conditions and traits comorbid with schizophrenia to identify traits as potential predictors and used LASSO regress ion to sel...
Source: Journal of NeuroImmune Pharmacology - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

Morphine Potentiates Dysbiotic Microbial and Metabolic Shifts in Acute SIV Infection
This study modeled early HIV infection by examining Simian Immunodeficiency Virus (SIV)-infected primates at 21  days or less both independently and in the context of opioid use. Fecal samples were analyzed both for 16S analysis of microbial populations as well as metabolite profiles via mass spectrometry. Our results indicate that changes are minor in SIV treated animals in the time points examined, however animals treated with morphine and SIV had significant changes in their microbial communities and metabolic profiles. This occurred in a time-independent fashion with morphine regardless of how long the animal had ...
Source: Journal of NeuroImmune Pharmacology - September 21, 2018 Category: Drugs & Pharmacology Source Type: research

Immunomodulatory Properties of Bone Marrow Mesenchymal Stem Cells from Patients with Amyotrophic Lateral Sclerosis and Healthy Donors
In this study, we aimed to compare the immunomodulatory properties of MSCs isolated from the bone marrow of patients suffering from ALS and healthy donors. Moreover, the influence of proinflammatory cytokines on the immunoregulatory functions of MSCs was also evaluated. We found that MSCs from ALS patients and healthy donors comparably affected mitogen-stimulated peripheral blood mononuclear cells and reduced the percentage of T helper (Th)1, Th17 and CD8+CD25+ lymphocytes. These MSCs also equally increased the percentage of Th2 and CD4+FOXP3+ T lymphocytes. On the other hand, MSCs from ALS patients decreased more strongly...
Source: Journal of NeuroImmune Pharmacology - September 21, 2018 Category: Drugs & Pharmacology Source Type: research

Morphine Potentiates Dysbiotic Microbial and Metabolic Shifts in Acute SIV Infection
This study modeled early HIV infection by examining Simian Immunodeficiency Virus (SIV)-infected primates at 21  days or less both independently and in the context of opioid use. Fecal samples were analyzed both for 16S analysis of microbial populations as well as metabolite profiles via mass spectrometry. Our results indicate that changes are minor in SIV treated animals in the time points examined, however animals treated with morphine and SIV had significant changes in their microbial communities and metabolic profiles. This occurred in a time-independent fashion with morphine regardless of how long the animal had ...
Source: Journal of NeuroImmune Pharmacology - September 21, 2018 Category: Drugs & Pharmacology Source Type: research

Immunomodulatory Properties of Bone Marrow Mesenchymal Stem Cells from Patients with Amyotrophic Lateral Sclerosis and Healthy Donors
In this study, we aimed to compare the immunomodulatory properties of MSCs isolated from the bone marrow of patients suffering from ALS and healthy donors. Moreover, the influence of proinflammatory cytokines on the immunoregulatory functions of MSCs was also evaluated. We found that MSCs from ALS patients and healthy donors comparably affected mitogen-stimulated peripheral blood mononuclear cells and reduced the percentage of T helper (Th)1, Th17 and CD8+CD25+ lymphocytes. These MSCs also equally increased the percentage of Th2 and CD4+FOXP3+ T lymphocytes. On the other hand, MSCs from ALS patients decreased more strongly...
Source: Journal of NeuroImmune Pharmacology - September 21, 2018 Category: Drugs & Pharmacology Source Type: research