MICROGLIA-PASSAGED SIMIAN IMMUNODEFICIENCY VIRUS INDUCES NEUROPHYSIOLOGICAL ABNORMALITIES IN MONKEYS

Four rhesus macaques were inoculated intravenously with a cryopreserve d stock of microglia obtained from a simian immunodeficiency virus (SI V)-infected rhesus macaque, Before infection, three of the four monkey s were trained and tested daily on a computerized neuropsychological t est battery, After SIV infection, behavioral testing continued to moni tor deficits associated with disease progression. Five additional age- matched, behaviorally trained monkeys served as controls, Neurophysiol ogical testing for visual and auditory evoked responses was accomplish ed 37-52 weeks after infection in all monkeys, Subsequently, all four SIV-infected monkeys and one control subject were sacrificed, and samp les of brain tissue were taken for pathological analysis, SIV-infected monkeys demonstrated abnormal responses in both auditory and visual e voked responses, In addition, around the time of electrophysiological recording, all three SIV-infected, behaviorally trained monkeys exhibi ted significant decreases in progressive-ratio performance, reflecting a reduction in reinforcer efficacy, One subject also demonstrated imp airments in shifting of attentional set and motor ability at that time , Neuropathological evaluation revealed that all four SIV-infected mon keys exhibited numerous perivascular and parenchymal infiltrating T ce lls, These findings document that SIV causes electrophysiological, beh avioral, and neuropathological sequelae similar to what has been obser ved in the human neuroAIDS syndrome, Our observations further validate the simian model for the investigation of the pathogenesis of AIDS de mentia and for the investigation of drugs with potential therapeutic b enefits.