首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Disruption of excitatory amino acid transporters in brains of SIV-infected rhesus macaques is associated with microglia activation
Authors:Meisner Falko  Neuen-Jacob Eva  Sopper Sieghart  Schmidt Michaela  Schlammes Serge  Scheller Carsten  Vosswinkel Daniel  Ter Meulen Volker  Riederer Peter  Koutsilieri Eleni
Institution:Institute of Virology and Immunobiology, University of Würzburg, Würzburg, Germany;
Institute of Neuropathology, University of Düsseldorf, Düsseldorf, Germany;
German Primate Center, Göttingen, Germany;
Clinical Neurochemistry (National Parkinson Foundation Center of Excellence Research Laboratory), Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany
Abstract:Glutamate-mediated neurodysfunction in human immunodeficiency virus (HIV) infection has been primarily suggested by in vitro studies. The regulation of glutamatergic neurotransmission in inflammation is a complex interaction between activation of immune mediators and adaptive changes in the functional elements of the glutamatergic synapse. We have used simian immunodeficiency virus (SIV)-infected macaques to answer the questions (i) whether perturbation of glutamate neurotransmission is evident during progression of immunodeficiency disease and (ii) what are the mechanisms underlying this impairment. Disease progression in SIV-infected macaques both in the periphery and in the brain was documented by clinical and general pathological examination, plasma and brain viral RNA load, T-cell analysis and brain histopathology. We report for the first time, disruption of excitatory amino acid transporters (EAATs), the cardinal glutamate clearing system, during SIV infection and a dramatic loss of EAATs associated with development of rapid acquired immunodeficiency syndrome (AIDS). EAATs impairment was correlated with activation status of microglia. Our data support the glutamate hypothesis for the development of HIV dementia and suggest that the pathogenetic mechanism for the neurodysfunction is the impairment of glutamate clearing which occurs in the stage of AIDS and which is associated with activated microglia.
Keywords:brain  dementia  excitatory amino acid transporters  glutamate  HIV  SIV
本文献已被 PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号