Bidirectional Associations among Nicotine and Tobacco Smoke, NeuroHIV, and Antiretroviral Therapy
AbstractPeople living with HIV (PLWH) in the antiretroviral therapy (ART) era may lose more life-years to tobacco use than to HIV. Yet, smoking rates are more than twice as high among PLWH than the general population, contributing not just to mortality but to other adverse health outcomes, including neurocognitive deficits (neuroHIV). There is growing evidence that synergy with chronic inflammation and immune dysregulation that persists despite ART may be one mechanism by which tobacco smoking contributes to neuroHIV. This review will summarize the differential effects of nicotine vs tobacco smoking on inflammation in addi...
Source: Journal of NeuroImmune Pharmacology - December 13, 2019 Category: Drugs & Pharmacology Source Type: research

Heroin Abuse and/or HIV Infection Dysregulate Plasma Exosomal miRNAs
AbstractExosomes play an important role in cell-to-cell communication as they can transfer functional molecules such as microRNAs (miRNAs) from one cell to another, exerting biological and immunological functions. Here, we investigated the impact of HIV infection and/or heroin use on the expression of the miRNAs in plasma exosomes. We found that HIV infection or heroin use upregulated the majority (98%) of a panel of plasma exosomal miRNAs associated with immune regulation and inflammation. We also observed the enhanced effect of HIV infection and heroin use on some of these upregulated miRNAs. Our further investigation sh...
Source: Journal of NeuroImmune Pharmacology - December 11, 2019 Category: Drugs & Pharmacology Source Type: research

Pre-exposure Prophylaxis Therapy and the Blood-Brain Barrier: Is PrEP Neuroprotective?
(Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - December 11, 2019 Category: Drugs & Pharmacology Source Type: research

Activation of the Protective Arm of the Renin Angiotensin System in Demyelinating Disease
AbstractThe renin angiotensin system (RAS), which is classically known for blood pressure regulation, has functions beyond this. There are two axes of RAS that work to counterbalance each other and are active throughout the body, including the CNS. The pathological axis, consisting of angiotensin II (A1-8), angiotensin converting enzyme (ACE) and the angiotensin II type 1 receptor (AT1R), is upregulated in many CNS diseases, including multiple sclerosis (MS). MS is an autoimmune and neurodegenerative disease of the CNS characterized by inflammation, demyelination and axonal degeneration. Published research has described in...
Source: Journal of NeuroImmune Pharmacology - December 11, 2019 Category: Drugs & Pharmacology Source Type: research

β-Adrenergic Signaling in Lung Cancer: A Potential Role for Beta-Blockers
AbstractLung cancer results in more patient deaths each year than any other cancer type. Additional treatment strategies are needed to improve clinical responses to approved treatment modalities and prevent the emergence of resistant disease. Catecholamines including norepinephrine and epinephrine are elevated as a result of chronic stress and mediate their physiological effects through activation of adrenergic receptors on target tissues. Lung cancer cells express β-adrenergic receptors (β-ARs), and numerous preclinical studies indicate that β2-AR signaling on lung cancer cells facilities cellular programs ...
Source: Journal of NeuroImmune Pharmacology - December 11, 2019 Category: Drugs & Pharmacology Source Type: research

CNS Neurotoxicity of Antiretrovirals
AbstractThe development of novel antiretroviral treatments has led to a significant turning point in the fight against HIV. Although therapy leads to virologic suppression and prolonged life expectancies, HIV-associated neurocognitive disorder (HAND) remains prevalent. While various hypotheses have been proposed to explain this phenomenon, a growing body of literature explores the neurotoxic effects of antiretroviral therapy. Research to date brings into question the potential role of such medications in neurocognitive and neuropsychiatric impairment seen in HIV-positive patients. This review highlights recent findings and...
Source: Journal of NeuroImmune Pharmacology - December 10, 2019 Category: Drugs & Pharmacology Source Type: research

Transmigration of Tetraspanin 2 (Tspan2) siRNA Via Microglia Derived Exosomes across the Blood Brain Barrier Modifies the Production of Immune Mediators by Microglia Cells
AbstractMicroglia are implicated in the neuropathogenesis of HIV. Tetraspanin 2 (Tspan2) is closely related to CD9 and CD81 proteins, and are expressed on microglia cells. They have been implicated in cell fusion and adhesion and in the immune response, and neuroinflammation. Developing therapeutics that target microglia remains a challenge as these therapeutics must cross the Blood-Brain Barrier (BBB). Our goal was to use microglia derived exosomes as a vehicle to deliver siRNA across the BBB to target human telomerase reverse transcriptase immortalized human microglial cells (HTHU) latently infected by HIV (HTHU-HIV) and...
Source: Journal of NeuroImmune Pharmacology - December 10, 2019 Category: Drugs & Pharmacology Source Type: research

Randomized, Placebo-Controlled Trial of Targeting Neuroinflammation with Ibudilast to Treat Methamphetamine Use Disorder
AbstractMethamphetamine (MA) triggers neuroinflammation and medications that counteract MA-induced neuroinflammation may reduce MA-induced neurodegeneration and improve neurocognition and treatment outcomes in MA use disorder. We performed a randomized, placebo-controlled trial to determine the safety and efficacy of ibudilast (IBUD), a phosphodiesterase inhibitor that reduces neuroinflammation, for the treatment of MA use disorder. Treatment-seeking volunteers with MA use disorder were randomly assigned to receive 12  weeks of IBUD 50 mg twice daily (N = 64) or placebo (N = 61) with m...
Source: Journal of NeuroImmune Pharmacology - December 9, 2019 Category: Drugs & Pharmacology Source Type: research

Treg Cells Attenuate Neuroinflammation and Protect Neurons in a Mouse Model of Parkinson ’s Disease
AbstractRegulatory T cells (Tregs), which secrete transforming growth factor (TGF)- β and interleukin (IL)-10, have essential role in anti-inflammatory and neurotrophic functions. Herein, we explore the neuroprotection of Tregs in Parkinson’s disease (PD) by adoptive transfer of Tregs. Tregs, isolated by magnetic sorting, were activated in vitro and then were adoptively transfer red to 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-treated mice. Neuroinflammation, dopaminergic neuronal loss and behavioral changes of PD mice were evaluated. Live cell imaging system detected a dynamic contact of Tregs with M...
Source: Journal of NeuroImmune Pharmacology - December 4, 2019 Category: Drugs & Pharmacology Source Type: research

Inhibition of the Dead Box RNA Helicase 3 Prevents HIV-1 Tat and Cocaine-Induced Neurotoxicity by Targeting Microglia Activation
AbstractHIV-1 Associated Neurocognitive Disorder (HAND) is a common and clinically detrimental complication of HIV infection. Viral proteins, including Tat, released from infected cells, cause neuronal toxicity. Substance abuse in HIV-infected patients greatly influences the severity of neuronal damage. To repurpose small molecule inhibitors for anti-HAND therapy, we employed MOLIERE, an AI-based literature mining system that we developed. All human genes were analyzed and prioritized by MOLIERE to find previously unknown targets connected to HAND. From the identified high priority genes, we narrowed the list to those with...
Source: Journal of NeuroImmune Pharmacology - December 4, 2019 Category: Drugs & Pharmacology Source Type: research

AGK2 Alleviates Lipopolysaccharide Induced Neuroinflammation through Regulation of Mitogen-Activated Protein Kinase Phosphatase-1
AbstractNeuroinflammation is associated with the progression of multiple neurological diseases. Many studies show that SIRT2 involves in multiple inflammatory processes. While, the mechanisms remain unclear. The purpose of this study was to explore the effect of SIRT2 inhibitor AGK2 on inflammatory responses and MAPK signaling pathways in LPS activated microglia in vitro and in vivo. The effect of AGK2 on cell viability of BV2 microglial cells was detected by CCK-8 assay. The expression of inflammatory cytokine iNOS was analyzed by western blotting and immunofluorescence. The mRNA expressions of iNOS, TNF- α, and IL-...
Source: Journal of NeuroImmune Pharmacology - November 30, 2019 Category: Drugs & Pharmacology Source Type: research

A Broad Application of CRISPR Cas9 in Infectious, Inflammatory and Neurodegenerative Diseases
AbstractBeing the most important immune-responsive cell type of the CNS, microglia always glorify the so-called crossroad of Neurology, Immunology and Pharmacology. As microglial activation is a hallmark of different neurodegenerative disorders including Alzheimer ’s disease (AD), Parkinson’s disease (PD), HIV-associated neurocognitive disorders (HAND), Amyotrophic lateral sclerosis (ALS), etc., selective targeting of microglial cell signaling may be a valid option to control these neurodegenerative disorders with lesser side effects. This is particularly important as no effective therapies are available agains...
Source: Journal of NeuroImmune Pharmacology - November 28, 2019 Category: Drugs & Pharmacology Source Type: research

Protease Inhibitors, Saquinavir and Darunavir, Inhibit Oligodendrocyte Maturation: Implications for Lysosomal Stress
AbstractDespite the introduction of antiretroviral (ARV) therapy (ART), approximately 30 –50% of people living with human immunodeficiency virus-1 (HIV-1) will develop a spectrum of measurable neurocognitive dysfunction, collectively called HIV-associated neurocognitive disorder (HAND). While the clinical manifestations of HAND have changed with the advent of ART, certain pathological features have endured, including white matter alterations and dysfunction. The persistence of white matter alterations in the post-ART era suggests that ARV drugs themselves may contribute to HAND pathology. Our group has previously dem...
Source: Journal of NeuroImmune Pharmacology - November 28, 2019 Category: Drugs & Pharmacology Source Type: research

Hemorrhage Associated Mechanisms of Neuroinflammation in Experimental Traumatic Brain Injury
AbstractTraumatic brain injury (TBI) is a major health problem for over 3.17 million people in the US, attracting increasing public attentions. Understanding the underlying mechanism of TBI is urgent for better diagnosis and treatment. Here, we examined the hypothesis that cerebral hemorrhagic coagulation and subsequent immune cells infiltration causes the progressive mechanisms of brain injury in moderate fluid percussion injury model. This represents a subdural hematoma and hemorrhagic head injury. We found increased hemorrhagic lesions and infarct volume in the injured brain with increment of pressure. The extent of hem...
Source: Journal of NeuroImmune Pharmacology - November 26, 2019 Category: Drugs & Pharmacology Source Type: research

Macrophage-Derived Extracellular Vesicles as Drug Delivery Systems for Triple Negative Breast Cancer (TNBC) Therapy
AbstractEfficient targeted delivery of anticancer agents to TNBC cells remains one of the greatest challenges to developing therapies. The lack of tumor-specific markers, aggressive nature of the tumor, and unique propensity to recur and metastasize make TNBC tumors more difficult to treat than other subtypes. We propose to exploit natural ability of macrophages to target cancer cells by means of extracellular vesicles (EVs) as drug delivery vehicles for chemotherapeutic agents, paclitaxel (PTX) and doxorubicin (Dox). We demonstrated earlier that macrophage-derived EVs loaded with PTX (EV-PTX) and Dox (EV-Dox) target cance...
Source: Journal of NeuroImmune Pharmacology - November 13, 2019 Category: Drugs & Pharmacology Source Type: research

Simvastatin Therapy in Multiple Sclerosis Patients with Respect to Gut Microbiome-Friend or Foe?
(Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - October 18, 2019 Category: Drugs & Pharmacology Source Type: research

Beta1- and Beta2-Adrenoceptors Expression Patterns in Human Non-small Cell Lung Cancer: Relationship with Cancer Histology
AbstractAssessment of Beta-AR protein expression on tumour tissues might be a plausible strategy to select cancer patients who can benefit from Beta-blockers therapy. The aim of this study is to evaluate the differences between resected tissue specimens from primary lung cancer (adenocarcinoma (ADC) and squamous cell carcinoma (SCC)) in terms of expression pattern of Beta1- and Beta2-AR in both tumour and adjacent surrounding non-tumour tissue. This retrospective study was based on the analysis of 80 patients with histologically confirmed diagnosis of primary Non-Small Cell Lung Cancer (NSCLC) who received surgical treatme...
Source: Journal of NeuroImmune Pharmacology - October 16, 2019 Category: Drugs & Pharmacology Source Type: research

Changes of Serum IgG Dimer Levels after Treatment with IVIg in Guillain-Barr é Syndrome
AbstractIntravenous immunoglobulins (IVIg) are standard treatment for Guillain-Barr é syndrome (GBS). Their exact mechanisms of action are versatile and not fully understood. One possible mechanism is neutralization of circulating autoantibodies via binding to anti- idiotypic antibodies forming idiotype-anti-idiotype dimeric IgG immune complexes. To examine the role of immune comp lex formation as mechanism of action for IVIg in GBS, 34 C57Bl/6 mice were either treated with anti-ganglioside antibodies and IVIg or IVIg and PBS alone, whereas eight additional mice were treated either with anti-ganglioside autoantibodi...
Source: Journal of NeuroImmune Pharmacology - September 12, 2019 Category: Drugs & Pharmacology Source Type: research

Modern Techniques for the Isolation of Extracellular Vesicles and Viruses
AbstractExtracellular signaling is pivotal to maintain organismal homeostasis. A quickly emerging field of interest within extracellular signaling is the study of extracellular vesicles (EV), which act as messaging vehicles for nucleic acids, proteins, metabolites, lipids, etc. from donor cells to recipient cells. This transfer of biologically active material within a vesicular body is similar to the infection of a cell through a virus particle, which transfers genetic material from one cell to another to preserve an infection state, and viruses are known to modulate EV. Although considerable heterogeneity exists within EV...
Source: Journal of NeuroImmune Pharmacology - September 12, 2019 Category: Drugs & Pharmacology Source Type: research

Evaluating Neurodevelopmental Consequences of Perinatal Exposure to Antiretroviral Drugs: Current Challenges and New Approaches
AbstractAs antiretroviral therapy (ART) becomes increasingly affordable and accessible to women of childbearing age across the globe, the number of children who are exposed to Human Immunodeficiency Viruses (HIV) but remain  uninfected is on the rise, almost all of whom were also exposed to ART perinatally. Although ART has successfully aided in the decline of mother-to-child-transmission of HIV, the long-term effects of in utero exposure to ART on fetal and postnatal neurodevelopment remain unclear. Evaluating the sa fety and efficacy of therapeutic drugs for pregnant women is a challenge due to the historic limitati...
Source: Journal of NeuroImmune Pharmacology - September 11, 2019 Category: Drugs & Pharmacology Source Type: research

A Broad Application of CRISPR Cas9 in Infectious Diseases of Central Nervous System
AbstractVirus-induced diseases or neurological complications are huge socio-economic burden to human health globally. The complexity of viral-mediated CNS pathology is exacerbated by reemergence of new pathogenic neurotropic viruses of high public relevance. Although the central nervous system is considered as an immune privileged organ and is mainly protected by barrier system, there are a vast majority of neurotropic viruses capable of gaining access and cause diseases. Despite continued growth of the patient population and a number of treatment strategies, there is no successful viral specific therapy available for vira...
Source: Journal of NeuroImmune Pharmacology - September 11, 2019 Category: Drugs & Pharmacology Source Type: research

Extracellular Vesicles as Drug Delivery Vehicles to the Central Nervous System
This article outlines the challenges in potential EV-based therapeutic delivery. (Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - September 4, 2019 Category: Drugs & Pharmacology Source Type: research

The Role of β-Blockers in Melanoma
AbstractMelanoma is one of the most aggressive and less chemotherapy-responsive human cancers, representing a major public health issue worldwide. The early diagnosis still represents the best approach in order to reduce mortality, especially in advanced stages. Preclinical evidence, collected through several in vitro and in vivo models, has been accumulating about the pathophysiological involvement of β-adrenoceptors in melanoma progression. This involvement has been paralleled by the evidence that drugs blocking β-adrenoceptors (β-blockers) may have a relevant role in the treatment of melanoma and in the p...
Source: Journal of NeuroImmune Pharmacology - September 3, 2019 Category: Drugs & Pharmacology Source Type: research

Strategies for the use of Extracellular Vesicles for the Delivery of Therapeutics
AbstractExtracellular vesicles (EVs) are nanosized, membrane-bound vesicles released from eukaryotic and prokaryotic cells that can transport cargo containing DNA, RNA, lipids and proteins, between cells as a means of intercellular communication. Although EVs were initially considered to be cellular debris deprived of any essential biological functions, emerging literature highlights the critical roles of EVs in the context of intercellular signaling, maintenance of tissue homeostasis, modulation of immune responses, inflammation, cancer progression, angiogenesis, and coagulation under both physiological and pathological s...
Source: Journal of NeuroImmune Pharmacology - August 27, 2019 Category: Drugs & Pharmacology Source Type: research

Host-Immune Interactions in JC Virus Reactivation and Development of Progressive Multifocal Leukoencephalopathy (PML)
AbstractWith the advent of immunomodulatory therapies and the HIV epidemic, the impact of JC Virus (JCV) on the public health system has grown significantly due to the increased incidence of Progressive Multifocal Leukoencephalopathy (PML). Currently, there are no pharmaceutical agents targeting JCV infection for the treatment and the prevention of viral reactivation leading to the development of PML. As JCV primarily reactivates in immunocompromised patients, it is proposed that the immune system (mainly the cellular-immunity component) plays a key role in the regulation of JCV to prevent productive infection and PML deve...
Source: Journal of NeuroImmune Pharmacology - August 27, 2019 Category: Drugs & Pharmacology Source Type: research

Low-Dose Subcutaneous Anti-CD20 Treatment Depletes Disease Relevant B Cell Subsets and Attenuates Neuroinflammation
AbstractTo explore the B cell depleting capacity of a low-dose (20  μg) subcutaneous mouse anti-CD20 antibody treatment on disease-relevant B cell populations within lymph nodes and the spleen. B cell depleting capacity was explored in healthy female C57BL/6 and BALB/c mice; following immune activation in two different mouse models: trinitrophenylated lipopolysac charide model (thymus-independent response) and dinitrophenyl-keyhole limpet hemocyanin model (thymus-dependent response); and in a chronic neuroinflammation experimental autoimmune encephalomyelitis model. CD20 protein expression on B cell subpopulations ...
Source: Journal of NeuroImmune Pharmacology - August 21, 2019 Category: Drugs & Pharmacology Source Type: research

HIV-1 Tat-Induced Astrocytic Extracellular Vesicle miR-7 Impairs Synaptic Architecture
AbstractAlthough combination antiretroviral therapy (cART) has improved the health of millions of those living with HIV-1 (Human Immunodeficiency Virus, Type 1), the penetration into the central nervous system (CNS) of many such therapies is limited, thereby resulting in residual neurocognitive impairment commonly referred to as NeuroHIV. Additionally, while cART has successfully suppressed peripheral viremia, cytotoxicity associated with the presence of viral Transactivator of transcription (Tat) protein in tissues such as the brain, remains a significant concern. Our previous study has demonstrated that both HIV-1 Tat as...
Source: Journal of NeuroImmune Pharmacology - August 10, 2019 Category: Drugs & Pharmacology Source Type: research

The Association of Immune Markers with Cognitive Performance in South African HIV-Positive Patients
AbstractDysregulated expression of neuro-immune markers has previously been linked to HIV-associated neurocognitive impairment. We undertook an exploratory approach in a HIV clade-C cohort, investigating the association between eight immune markers and neurocognitive performance in 99 HIV+ and 51 HIV- participants. Markers were selected on preliminary and putative evidence of their link to key neuro-immune functions. Cognitive performance was established using a battery of tests sensitive to HIV-associated neurocognitive impairment, with domain-based scores utilized in analysis. The markers Thymidine phosphorylase (TYMP) a...
Source: Journal of NeuroImmune Pharmacology - August 6, 2019 Category: Drugs & Pharmacology Source Type: research

Beneficial and Adverse Effects of cART Affect Neurocognitive Function in HIV-1 Infection: Balancing Viral Suppression against Neuronal Stress and Injury
AbstractHIV-associated neurocognitive disorders (HAND) persist despite the successful introduction of combination antiretroviral therapy (cART). While insufficient concentration of certain antiretrovirals (ARV) may lead to incomplete viral suppression in the brain, many ARVs are found to cause neuropsychiatric adverse effects, indicating their penetration into the central nervous system (CNS). Several lines of evidence suggest shared critical roles of oxidative and endoplasmic reticulum stress, compromised neuronal energy homeostasis, and autophagy in the promotion of neuronal dysfunction associated with both HIV-1 infecti...
Source: Journal of NeuroImmune Pharmacology - August 6, 2019 Category: Drugs & Pharmacology Source Type: research

Inhibitory Control Deficits Associated with Upregulation of CB 1 R in the HIV-1 Tat Transgenic Mouse Model of Hand
AbstractIn the era of combined antiretroviral therapy, HIV-1 infected individuals are living longer lives; however, longevity is met with an increasing number of HIV-1 associated neurocognitive disorders (HAND) diagnoses. The transactivator of transcription (Tat) is known to mediate the neurotoxic effects in HAND by acting directly on neurons and also indirectly via its actions on glia. The Go/No-Go (GNG) task was used to examine HAND in the Tat transgenic mouse model. The GNG task involves subjects discriminating between two stimuli sets in order to determine whether or not to inhibit a previously trained response. Data r...
Source: Journal of NeuroImmune Pharmacology - August 1, 2019 Category: Drugs & Pharmacology Source Type: research

Stem Cell Extracellular Vesicles and their Potential to Contribute to the Repair of Damaged CNS Cells
AbstractNeurological diseases and disorders are leading causes of death and disability worldwide. Many of these pathologies are associated with high levels of neuroinflammation and irreparable tissue damage. As the global burden of these pathologies continues to rise there is a significant need for the development of novel therapeutics. Due to their multipotent properties, stem cells have broad applications for tissue repair; additionally, stem cells have been shown to possess both immunomodulatory and neuroprotective properties. It is now believed that paracrine factors, such as extracellular vesicles (EVs), play a critic...
Source: Journal of NeuroImmune Pharmacology - July 24, 2019 Category: Drugs & Pharmacology Source Type: research

Antiretroviral Drugs Promote Amyloidogenesis by De-Acidifying Endolysosomes
AbstractAntiretroviral therapeutics (ART) have effectively increased the long-term survival of HIV-1 infected individuals. However, the prevalence of HIV-1 associated neurocognitive disorders (HAND) has increased and so too have clinical manifestations and pathological features of Alzheimer ’s disease (AD) in people living with HIV-1/AIDS. Although underlying mechanisms are not clear, chronic exposure to ART drugs has been implicated in the development of AD-like symptoms and pathology. ART drugs are categorized according to their mechanism of action in controlling HIV-1 levels. All ART drugs are organic compounds th...
Source: Journal of NeuroImmune Pharmacology - July 23, 2019 Category: Drugs & Pharmacology Source Type: research

Intranasal Delivery of lincRNA-Cox2 siRNA Loaded Extracellular Vesicles Decreases Lipopolysaccharide-Induced Microglial Proliferation in Mice
In this study, we found thatlincRNA-Cox2 controls the expression of a set of cell cycle genes in lipopolysaccharide (LPS)-stimulated microglial cells. Our in vitro study suggested that knocking downlincRNA-Cox2 reversed LPS-induced microglial proliferation. In addition, our in vivo study demonstrated that intranasally delivered lincRNA-Cox2-siRNA loaded EVs could reach the brain resulting in a significant decrease in the expression oflincRNA-Cox2 in the microglia. Importantly, lincRNA-Cox2-siRNA loaded EVs also decreased LPS-induced microglial proliferation in mice. These findings indicate that intranasal delivery of EV-lo...
Source: Journal of NeuroImmune Pharmacology - July 20, 2019 Category: Drugs & Pharmacology Source Type: research

Neuroprotective Effects of Genistein in a SOD1-G93A Transgenic Mouse Model of Amyotrophic Lateral Sclerosis
AbstractOxidant toxicity has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), an insidiously progressive neurodegenerative disorder involving upper and lower motor neurons. Here, we investigated the cellular and molecular mechanisms underlying the neuroprotective effects of an anti-oxidant genistein in SOD1-G93A transgenic mouse model of ALS. Rotarod test, hanging wire test and hindlimb clasping test were used to determined disease onset and assess motor performance. Immunostaining together with neuronal size measurement were used to count viable motor neurons. In addition, immunostaining procedu...
Source: Journal of NeuroImmune Pharmacology - July 18, 2019 Category: Drugs & Pharmacology Source Type: research

Dopaminergic Pathways in Obesity-Associated Inflammation
We present an explanatory hypothesis with a model that integrate central and peripheral dopaminergic circuits in the relationship between neuroimmune and metabolic systems in obesity-associated inflammation. A perspective on the potential role of dopaminergic drugs in the context of obesity will be given.Graphical AbstractGraphical representation of central and peripheral dopaminergic pathways in obesity-associated inflammation (Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - July 17, 2019 Category: Drugs & Pharmacology Source Type: research

Overexpression of TIPE2, a Negative Regulator of Innate and Adaptive Immunity, Attenuates Cognitive Deficits in APP/PS1 Mice
In this study, we compared the gene and protein expres sions of TIPE2 between the APP/PS1 mice and the age-matched wild type (WT) mice at different stages of development using western blot and RT-qPCR. The hippocampal expression of the TIPE2 mRNA and protein in APP/PS1 mice was higher than that of the WT mice starting from 6 months to 10 months. Howev er, the difference of the TIPE2 expression between the APP/PS1 mice and the WT mice declined in a time-dependent manner. The spatial learning and memory deficit from the 8-month-old APP/PS1 mice was observed in the Y-maze test and fear conditioning task. Interesting...
Source: Journal of NeuroImmune Pharmacology - July 8, 2019 Category: Drugs & Pharmacology Source Type: research

Haloperidol Reduces the Activity of Complement and Induces the Anti-Inflammatory Transformation of Peritoneal Macrophages in Rats
AbstractIt is known that psychotropic substances affect the immune system. Unfortunately, chronic antipsychotic administration causes side toxicological effects, associated with oxidative stress. The mechanisms of these effects are still unclear. We investigated the impact of sub-chronic administration of haloperidol (Hal) on parameters of innate immunity and related systems in healthy rats and compared them with Hal content. Hal administration (0.5  mg/kg, 3 weeks) resulted in two-fold decrease of the activity of the complement system and hemostasis. Hal content correlated with the activity of the complement (r&...
Source: Journal of NeuroImmune Pharmacology - July 6, 2019 Category: Drugs & Pharmacology Source Type: research

Cerebral Vascular Toxicity of Antiretroviral Therapy
AbstractHIV infection is associated with comorbidities that are likely to be driven not only by HIV itself, but also by the toxicity of long-term use of antiretroviral therapy (ART). Indeed, increasing evidence demonstrates that the antiretroviral drugs used for HIV treatment have toxic effects resulting in various cellular and tissue pathologies. The blood-brain barrier (BBB) is a modulated anatomophysiological interface which separates and controls substance exchange between the blood and the brain parenchyma; therefore, it is particularly exposed to ART-induced toxicity. Balancing the health risks and gains of ART has t...
Source: Journal of NeuroImmune Pharmacology - June 17, 2019 Category: Drugs & Pharmacology Source Type: research

Glutamine Antagonist JHU083 Normalizes Aberrant Glutamate Production and Cognitive Deficits in the EcoHIV Murine Model of HIV-Associated Neurocognitive Disorders
AbstractHIV-associated neurocognitive disorders (HAND) have been linked to dysregulation of glutamate metabolism in the central nervous system (CNS) culminating in elevated extracellular glutamate and disrupted glutamatergic neurotransmission. Increased glutamate synthesis via upregulation of glutaminase (GLS) activity in brain immune cells has been identified as one potential source of excess glutamate in HAND. However, direct evidence for this hypothesis in an animal model is lacking, and the viability of GLS as a drug target has not been explored. In this brief report, we demonstrate that GLS inhibition with the glutami...
Source: Journal of NeuroImmune Pharmacology - June 17, 2019 Category: Drugs & Pharmacology Source Type: research

Cas9 Ribonucleoprotein Complex Delivery: Methods and Applications for Neuroinflammation
AbstractThe CRISPR/Cas9 system is a revolutionary gene editing technology that combines simplicity of use and efficiency of mutagenesis. As this technology progresses toward human therapies, valid concerns including off-target mutations and immunogenicity must be addressed. One approach to address these issues is to minimize the presence of the CRISPR/Cas9 components by maintaining a tighter temporal control of Cas9 endonuclease and reducing the time period of activity. This has been achieved to some degree by delivering the CRISPR/Cas9 system via pre-formed Cas9  + gRNA ribonucleoprotein (RNP) complexes. In ...
Source: Journal of NeuroImmune Pharmacology - June 6, 2019 Category: Drugs & Pharmacology Source Type: research

Involvement of Interferon Regulatory Factor 7 in Nicotine ’s Suppression of Antiviral Immune Responses
AbstractNicotine, the active ingredient in tobacco smoke, suppresses antiviral responses. Interferon regulatory factors (IRFs) regulate transcription of type I interferons (IFNs) and IFN-stimulated genes (ISGs) in this response. IRF7 is a key member of the IRF family. Expression ofIrf7 is elevated in the brains of virus-infected animals, including human immunodeficiency virus-1 transgenic (HIV-1Tg) rats. We hypothesized that IRF7 affects nicotine ’s modulation of antiviral responses. Using CRISPR/Cas9 system,IRF7-mutant cell lines were created from human embryonic kidney 293FT cells in which 16 nicotinic acetylcholin...
Source: Journal of NeuroImmune Pharmacology - June 1, 2019 Category: Drugs & Pharmacology Source Type: research

Cinnamon and its Metabolite Protect the Nigrostriatum in a Mouse Model of Parkinson ’s Disease Via Astrocytic GDNF
This study underlines the importance of sodium benzoate (NaB), a metabolite of commonly-used spice cinnamon, a food-additive and an FDA-approved drug against hyperammonemia, in stimulating GDNF in primary mouse and human astrocytes. Presence of cAMP response element (CRE) in theGdnf gene promoter, recruitment of CREB to theGdnf promoter by NaB and abrogation of NaB-mediated GDNF expression by siRNA knockdown of CREB suggest that NaB induces the transcription ofGdnf via CREB. Finally, oral administration of NaB and cinnamon itself increased the level of GDNF in vivo in the substantia nigra pars compacta (SNpc) of normal as ...
Source: Journal of NeuroImmune Pharmacology - May 22, 2019 Category: Drugs & Pharmacology Source Type: research

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