Phospholipase A(2)(PLA(2)) enzymes are considered the primary source of arachidonic acid for cyclooxygenase (COX)-mediated biosynthesis prostaglandins. Here, we show that a distinct pathway exists in brain, where monoacylglycerol lipase (MAGL) hydrolyzes endocannabinoid 2-arachidonoylglycerol to generate major arachidonate precursor pool neuroinflammatory MAGL-disrupted animals neuroprotection parkinsonian mouse model. These spared hemorrhaging caused by COX inhibitors gut, prostaglandins...

Abstract Strong evidence supports that CNS-specific CD4+ T cells are central to the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Using a model spontaneous EAE, we demonstrated myelin basic protein (MBP)-specific up-regulate activation markers in CNS-draining cervical lymph nodes at time when there is no cell anywhere else, including CNS, before appearance clinical signs. In number MBP-specific numbers does not build up gradually CNS; instead, swift...

One of the consequences HIV infection is damage to CNS. To characterize virologic, immunologic, and functional factors involved in HIV-induced CNS disease, we analyzed viral loads T cell infiltrates brains SIV-infected rhesus monkeys whose function (sensory evoked potential) was impaired. Following infection, potentials were abnormal, indicating early disease. Upon autopsy at 11 wk post-SIV inoculation, infected animals contained over 5-fold more CD8(+) cells than did uninfected controls. In...

Abstract Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the CNS initiated by autoreactive CD4+ T cells. EAE classically presents with a progressive ascending paralysis and model multiple sclerosis that recapitulates some aspects disease. In this report we describe mouse strain spontaneously develops severe, nonclassical form 100% incidence. The distinct clinical phenotype marked initially slight head tilt, progressing to severe spinning, or rotatory motion....

MicroRNA (miR)-142 is up-regulated in the brain HIV and SIV encephalitis (SIVE). We identified cell types where miR-142 its relevant downstream target. Fluorescent situ hybridization combined with immunofluorescent labeling revealed that miR-142-3p -5p are expressed within hippocampal neurons myeloid cells SIVE. Sirtuin1 (SIRT1) was predicted as a potential target by analysis of 3'-UTR bioinformatic factors linked to altered gene expression profile Overexpression pre-miR-142 HEK293T led...

Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within Central Nervous System (CNS). Within CNS, Meth has ability modify activity/function innate immune cells and increase brain viral loads. Here, we examined changes in gene expression profile neuron-free microglial cell preparations isolated from macaques infected with Simian Immunodeficiency Virus (SIV), model neuroAIDS, exposed Meth. We aimed identify molecular...

Astrocyte activation is one of the earliest findings in brain methamphetamine (Meth) abusers. Our goal this study was to identify characteristics astrocytic acute response drug, which may be critical pathogenic outcomes secondary use. We developed an integrated analysis gene expression data changes caused by direct exposure Meth treatment astrocytes vitro, and better understand how respond, what are early molecular markers associated with response. examined literature search similar...

The Human Immunodeficiency Virus (HIV) infects cells in the Central Nervous System (CNS), where access of antiretrovirals and antibodies that can kill virus may be challenging. As a result early HIV entry brain, infected individuals develop inflammation neurological deficits at various levels, which are aggravated by drugs abuse. In non-human primate model HIV, we have previously shown abuse such as Methamphetamine (Meth) increase brain viral load correlation with higher number...

Abstract The host reaction to infection of the brain contributes a number CNS pathologies including neuro-AIDS. In this study, we have identified accumulation SIV-specific CTL in brains SIV-infected animals who neurophysiological abnormalities but are otherwise asymptomatic. enter early after viral and maintained even when those reactive with an immunodominant epitope Tat lost from rest body. specialized environment unique outcome. Following SIV infection, levels IL-15 were significantly...

The use of China-derived monkeys in AIDS research has been limited by reports reduced susceptibility to SIV. We performed a serial passage SIV Chinese macaques, which resulted viral stock capable inducing simian and high levels replication these animals. Similar HIV humans, pathogenesis non-human primates is not geographical origin. macaques are useful pathogenesis, vaccine, therapeutic studies AIDS.

Abstract It has become increasingly apparent in studies of mutant mice and observations disease that cytokine production by fully committed effector T cells within the Th1 Th2 phenotype can vary each group. This potentially influence type effectiveness a given immune response. The factors responsible for inducing variable subtype responses have not been well established. Using transgenic expressing myelin basic protein-specific TCR, we demonstrate here two distinct populations are...

Human immunodeficiency virus (HIV)-associated dementia (HAD) is a syndrome occurring in HIV-infected patients with advanced disease that likely develops as result of macrophage and microglial activation well other immune events triggered by the central nervous system. The most relevant experimental model HAD, rhesus macaques exhibiting simian (SIV) encephalitis (SIVE), closely reproduces human has been successfully used to advance our understanding mechanisms underlying HAD. In this study we...

Alcohol consumption is a common problem in HIV-infected individuals, and the effects of alcohol may alter efficiency immune response, potentially aggravating disease as well affecting end organs, such brain. However, elements virus-host interaction that are modulated by ethanol poorly dissected.Ethanol intake was conditioned rhesus macaques prior to SIV infection, order mimic this human behavior, allow evaluation aspects virus-immune system interactions during acute time-points, when...

Hyperthermia is a potentially lethal side effect of Methamphetamine (Meth) abuse, which involves the participation peripheral thermogenic sites such as Brown Adipose Tissue (BAT). In previous study we found that anti-oxidant N-acetyl cysteine (NAC) can prevent high increase in temperature mouse model Meth-hyperthermia. Here, have further explored ability NAC to modulate Meth-induced hyperthermia correlation with changes BAT. We treatment controls causes hypothermia, and, when administered...

Objective: Methamphetamine and cannabis are two widely used substances among people living with HIV (PLWH). Whereas methamphetamine use has been found to worsen HIV-associated neurocognitive impairment, the effects of combined disorder on neurocognition in PLWH not understood. In present study, we aimed determine influence these substance disorders explore if methamphetamine-cannabis interacted status. Method Participants: After completing a comprehensive neurobehavioral assessment, (n =...

ABSTRACT The human immunodeficiency virus type 1-associated cognitive-motor disorder, including the AIDS dementia complex, is characterized by brain functional abnormalities that are associated with injury initiated viral infection of brain. Indoleamine 2,3-dioxygenase (IDO), first and rate-limiting enzyme in tryptophan catabolism extrahepatic tissues, can lead to neurotoxicity through generation quinolinic acid immunosuppression alter chemistry via depletion tryptophan. Using simian...

CNS abnormalities can be detected during chronic human immunodeficiency virus (HIV) infection, before the development of opportunistic infections or other sequelae immunodeficiency. However, although end-stage dementia caused by HIV has been linked to presence infected and activated macrophages microglia in brain, nature changes resulting motor cognitive disorders stage is unknown. Using simian virus-infected rhesus monkeys, we sought molecular basis for dysfunction. In stable stage, nearly...