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Lu Cao, Mingui Fu, Santosh Kumar, Anil Kumar
Methamphetamine (METH), a commonly used controlled substance, is known to exacerbate neuropathological dysfunction in HIV-infected individuals. The neuropathological manifestation results from cell death or dysfunction in the central nervous system (CNS) wherein autophagy is expected to have an important role. Autophagy is generally considered protective during deprivation/stress. However, excessive autophagy can be destructive, leading to autophagic cell death. This study was designed to investigate if METH and HIV-1 gp120 interact to induce autophagy in SVGA astrocytes, and whether autophagy is epiphenomenal or it has a role in METH- and gp120-induced cytotoxicity...
October 20, 2016: Cell Death & Disease
Mahar Fatima, Bharat Prajapati, Kanza Saleem, Rina Kumari, Chitra Mohindar Singh Singal, Pankaj Seth
Astroglia are indispensable component of the tripartite synapse ensheathing innumerous soma and synapses. Its proximity to neurons aids the regulation of neuronal functions, health and survival through dynamic neuroglia crosstalk. Susceptibility of astrocyte to HIV-1 infection and subsequent latency culminates in compromised neuronal health. The viral protein HIV-1 transactivator of transcription (Tat) is neurotoxic. HIV-1 Tat is detected in brain of AIDS patients even in cases where viral load is non-detectable due to successful HAART therapy...
October 20, 2016: Glia
Chung-Ching Chio, Mao-Tsun Lin, Ching-Ping Chang, Hung-Jung Lin
BACKGROUND: Transforming growth factor-beta 1 (TGF-β1) regulates many processes after traumatic brain injury (TBI). Both Neuro AiD(™) (MLC601) and Astragaloside (AST) attenuate microglia activation in rats with TBI. The purpose of this study was to investigate whether MLC601 or AST improves output of TBI by affecting microglial expression of TGF-β1. MATERIALS AND METHODS: Adult male Sprague-Dawley rats (120 in number) were used to investigate the contribution of TGF-β1-containing microglia in the MLC601-mediated or the AST-mediated neuroprotection in the brain trauma condition using lateral fluid-percussion injury...
October 19, 2016: European Journal of Clinical Investigation
Christopher K Arnatt, Bethany A Falls, Yunyun Yuan, Thomas J Raborg, Ruturaj R Masvekar, Nazira El-Hage, Dana E Selley, Anthony V Nicola, Pamela E Knapp, Kurt F Hauser, Yan Zhang
Modern antiretroviral therapies have provided HIV-1 infected patients longer lifespans and better quality of life. However, several neurological complications are now being seen in these patients due to HIV-1 associated injury of neurons by infected microglia and astrocytes. In addition, these effects can be further exacerbated with opiate use and abuse. One possible mechanism for such potentiation effects of opiates is the interaction of the mu opioid receptor (MOR) with the chemokine receptor CCR5 (CCR5), a known HIV-1 co-receptor, to form MOR-CCR5 heterodimer...
September 26, 2016: Bioorganic & Medicinal Chemistry
Yan Fan, Johnny J He
HIV-1 Tat is a major culprit for HIV/neuroAIDS. One of the consistent hallmarks of HIV/neuroAIDS is reactive astrocytes or astrocytosis, characterized by increased cytoplasmic accumulation of the intermediate filament glial fibrillary acidic protein (GFAP). We have shown that that Tat induces GFAP expression in astrocytes and that GFAP activation is indispensible for astrocyte-mediated Tat neurotoxicity. However, the underlying molecular mechanisms are not known. In this study, we showed that Tat expression or GFAP expression led to formation of GFAP aggregates and induction of unfold protein response (UPR) and endoplasmic reticulum (ER) stress in astrocytes...
September 8, 2016: Journal of Biological Chemistry
Yan Fan, Johnny J He
Tat interaction with astrocytes has been shown to be important for Tat neurotoxicity and HIV/neuroAIDS. We have recently shown that Tat expression leads to increased glial fibrillary acidic protein (GFAP) expression and aggregation and activation of unfolded protein response/endoplasmic reticulum stress in astrocytes and causes neurotoxicity. However, the exact molecular mechanisms of astrocyte-mediated Tat neurotoxicity is not defined. In this study, we showed that neurotoxic factors other than Tat protein itself were present in the supernatant of Tat-expressing astrocytes...
September 8, 2016: Journal of Biological Chemistry
Kenneth Williams, Andrew Lackner, Jaclyn Mallard
Non-human primate models of AIDS and neuroAIDS are the premiere model of HIV infection of the CNS and neuropathogenesis. This review discusses current SIV infection models of neuroAIDS emphasizing findings in the last two years. Consistent in these findings is the interplay between host factors that regulate immune responses to virus and viral replication. Several rapid models of AIDS with consistent CNS pathogenesis exist, each of which modulates by antibody treatment or viruses that cause rapid immune suppression and replicate well in macrophages...
August 2016: Current Opinion in Virology
Thangavel Samikkannu, Venkata S R Atluri, Madhavan P N Nair
HIV infection and cocaine use have been identified as risk factors for triggering neuronal dysfunction. In the central nervous system (CNS), energy resource and metabolic function are regulated by astroglia. Glia is the major reservoir of HIV infection and disease progression in CNS. However, the role of cocaine in accelerating HIV associated energy deficit and its impact on neuronal dysfunction has not been elucidated yet. The aim of this study is to elucidate the molecular mechanism of HIV associated neuropathogenesis in cocaine abuse and how it accelerates the energy sensor AMPKs and its subsequent effect on mitochondrial oxidative phosphorylation (OXPHOS), BRSKs, CDC25B/C, MAP/Tau, Wee1 and epigenetics remodeling complex SWI/SNF...
2016: Scientific Reports
Shilpa Buch, Ernest T Chivero, Jackie Hoare, Jibreel Jumare, Noeline Nakasujja, Victor Mudenda, Robert Paul, Georgette D Kanmogne, Ned Sacktor, Charles Wood, Walter Royal, Jeymohan Joseph
Despite major advances in HIV-1 treatment, the prevalence of HIV-associated neurocognitive disorders (HAND) remains a problem, particularly as individuals on suppressive treatment continue to live longer. To facilitate discussion on emerging and future directions in HAND research, a meeting was held in Durban, South Africa in March 2015 as part of the Society of Neuroscientists of Africa (SONA) conference. The objective of the meeting was to assess the impact of HIV subtype diversity on HAND and immunological dysfunction...
October 2016: Journal of Neurovirology
Natasha L Fabiaña, Christopher L H Chen, Narayanaswamy Venketasubramanian, Chun Fan Lee, K S Lawrence Wong, Deidre Anne De Silva
In the randomized controlled trial of NeuroAiD versus placebo following ischemic stroke, there was a trend for sex influencing the treatment effect of NeuroAiD in improving functional outcome following ischemic stroke (p=0.075).
November 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Nicoletta Ciccarelli, Silio Limiti, Massimiliano Fabbiani, Eleonora Baldonero, Benedetta Milanini, Silvia Lamonica, Roberto Cauda, Simona Di Giambenedetto, Maria Caterina Silveri
HIV+ population is getting older because of progress in treatments. Yet, there are concerns that Older HIV+ individuals (OHIV+) may be more vulnerable for developing a "cortical" dementia such as Alzheimer Disease (AD). Our aim was to explore the hypothesis that the cognitive deficit extends to ''cortical'' functions in OHIV+ by comparing serial position effects (SPE) in different groups of participants affected by "cortical" or "subcortical" damage. We enrolled a total of 122 subjects: 22 OHIV+ (≥60 years of age), 31 Younger HIV+ (YHIV+) (<60 years of age), 18 participants with AD, 23 subjects with Parkinson Disease (PD), and 28 healthy subjects...
June 13, 2016: Applied Neuropsychology. Adult
R D Jayant, M Nair
No abstract text is available yet for this article.
March 2016: Journal of biosensors & bioelectronics
Norma Kabuba, J Anitha Menon, Donald R Franklin, Robert K Heaton, Knut A Hestad
This is a study of neuroAIDS in sub-Saharan Africa, involving 266 Zambian adults infected with the human immunodeficiency virus (HIV), clade C. All HIV+ participants were receiving combination antiretroviral therapy (CART), and were administered a comprehensive neuropsychological (NP) test battery covering seven ability domains that are frequently affected by neuroAIDS. The battery was developed in the U.S. but has been validated in other international settings and has demographically-corrected normative standards based upon 324 healthy Zambian adults...
June 8, 2016: AIDS and Behavior
Prasun K Datta, Satish Deshmane, Kamel Khalili, Salim Merali, John C Gordon, Chiara Fecchio, Carlos A Barrero
HIV-1 infected macrophages play a significant role in the neuropathogenesis of AIDS. HIV-1 viral protein R (Vpr) not only facilitates HIV-1 infection but also contribute to long-lived persistence in macrophages. Our previous studies using SILAC-based proteomic analysis showed that the expression of critical metabolic enzymes in the glycolytic pathway and tricarboxylic acid (TCA) cycle were altered in response to Vpr expression in macrophages. We hypothesized that Vpr-induced modulation of glycolysis and TCA cycle regulates glutamate metabolism and release in HIV-1 infected macrophages...
September 2016: Cell Cycle
Vidya Sagar, Venkata Subba Rao Atluri, Sudheesh Pilakka-Kanthikeel, Madhavan Nair
The human immunodeficiency virus (HIV) is a neurotropic virus. It induces neurotoxicity and subsequent brain pathologies in different brain cells. Addiction to recreational drugs remarkably affects the initiation of HIV infections and expedites the progression of acquired immunodeficiency syndrome (AIDS) associated neuropathogenesis. Symptoms of HIV-associated neurocognitive disorders (HAND) are noticed in many AIDS patients. At least 50 % of HIV diagnosed cases show one or other kind of neuropathological signs or symptoms during different stages of disease progression...
2016: Molecular Brain
Marie-Josée Brouillette, Tracy Yuen, Lesley K Fellows, Lucette A Cysique, Robert K Heaton, Nancy E Mayo
INTRODUCTION: While HIV-associated neurocognitive impairment remains common despite the widespread use of combined antiretroviral therapy (cART), there have been relatively few studies investigating the trajectories of neurocognitive change in longitudinal NeuroAIDS studies. OBJECTIVE: To estimate the magnitude and pattern of neurocognitive change over the first 3 years of follow-up using Group-Based Trajectory Analysis (GBTA) applied to participants in the longitudinal arm of the CHARTER cohort...
2016: PloS One
Martyn K White, Rafal Kaminski, Hassen Wollebo, Wenhui Hu, Thomas Malcolm, Kamel Khalili
The study of neurological infections by viruses defines the field of neurovirology, which has emerged in the last 30 years and was founded upon the discovery of a number of viruses capable of infecting the human nervous system. Studies have focused on the molecular and biological basis of viral neurological diseases with the aim of revealing new therapeutic options. The first studies of neurovirological infections can be traced back to the discovery that some viruses have an affinity for the nervous system with research into rabies by Louis Pasteur and others in the 1880s...
July 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Malay K Das, Anupam Sarma, Tapash Chakraborty
Human immunodeficiency virus (HIV) is a neurotropic virus that enters the central nervous system (CNS) early in the course of infection. Although highly active antiretroviral therapy (HAART) has resulted in remarkable decline in the morbidity and mortality in AIDS patients, controlling HIV infections still remains a global health priority. HIV access to the CNS serves as the natural viral preserve because most antiretroviral (ARV) drugs possess inadequate or zero delivery across the brain barriers. The structure of the blood-brain barrier (BBB), the presence of efflux pumps, and the expression of metabolic enzymes pose hurdles for ARV drug-brain entry...
October 2016: Drug Delivery and Translational Research
Brittany D Rife, David J Nolan, Susanna L Lamers, Patrick Autissier, Tricia Burdo, Kenneth C Williams, Marco Salemi
UNLABELLED: The emergence of a distinct subpopulation of human or simian immunodeficiency virus (HIV/SIV) sequences within the brain (compartmentalization) during infection is hypothesized to be linked to AIDS-related central nervous system (CNS) neuropathology. However, the exact evolutionary mechanism responsible for HIV/SIV brain compartmentalization has not been thoroughly investigated. Using extensive viral sampling from several different peripheral tissues and cell types and from three distinct regions within the brain from two well-characterized rhesus macaque models of the neurological complications of HIV infection (neuroAIDS), we have been able to perform in-depth evolutionary analyses that have been unattainable in HIV-infected subjects...
July 1, 2016: Journal of Virology
Qiang Wei, Li Liu, Zhe Cong, Xiaoxian Wu, Hui Wang, Chuan Qin, Patricia Molina, Zhiwei Chen
Delta9-tetrahydrocannabinol (Δ(9)-THC) is the major psychoactive component of the cannabis plant. Δ(9)-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 Δ(9)-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 Δ(9)-THC administration using 0...
September 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
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