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Microglia-passaged simian immunodeficiency virus induces neurophysiological abnormalities in monkeys
O Prospéro-García1, L H Gold, H S Fox
1Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
Abstract:
Four rhesus macaques were inoculated intravenously with a cryopreserved stock of microglia obtained from a simian immunodeficiency virus (SIV)-infected rhesus macaque. Before infection, three of the four monkeys were trained and tested daily on a computerized neuropsychological test battery. After SIV infection, behavioral testing continued to monitor deficits associated with disease progression. Five additional age-matched, behaviorally trained monkeys served as controls. Neurophysiological testing for visual and auditory evoked responses was accomplished 37-52 weeks after infection in all monkeys. Subsequently, all four SIV-infected monkeys and one control subject were sacrificed, and samples of brain tissue were taken for pathological analysis. SIV-infected monkeys demonstrated abnormal responses in both auditory and visual evoked responses. In addition, around the time of electrophysiological recording, all three SIV-infected, behaviorally trained monkeys exhibited significant decreases in progressive-ratio performance, reflecting a reduction in reinforcer efficacy. One subject also demonstrated impairments in shifting of attentional set and motor ability at that time. Neuropathological evaluation revealed that all four SIV-infected monkeys exhibited numerous perivascular and parenchymal infiltrating T cells. These findings document that SIV causes electrophysiological, behavioral, and neuropathological sequelae similar to what has been observed in the human neuroAIDS syndrome. Our observations further validate the simian model for the investigation of the pathogenesis of AIDS dementia and for the investigation of drugs with potential therapeutic benefits.
Insights
Simian immunodeficiency virus (SIV) infection in macaques caused neurological and behavioral deficits, mimicking human neuroAIDS. This study validates the macaque model for studying AIDS dementia and potential therapeutics.
Area of Science:
- Neuroscience
- Immunology
- Primatology
Background:
- The simian immunodeficiency virus (SIV) model is crucial for understanding human neurodegenerative diseases like AIDS dementia.
- Investigating SIV-induced neurological sequelae in macaques offers insights into pathogenesis and therapeutic strategies.
Purpose of the Study:
- To document the electrophysiological, behavioral, and neuropathological effects of SIV infection in rhesus macaques.
- To validate the use of SIV-infected macaques as a model for human neuroAIDS.
Main Methods:
- Four rhesus macaques were intravenously inoculated with SIV; three were behaviorally trained and tested before and after infection.
- Neurophysiological testing (visual and auditory evoked responses) and neuropathological analysis of brain tissue were performed.
- Control group of five age-matched, behaviorally trained macaques was used for comparison.
Main Results:
- SIV-infected macaques showed abnormal auditory and visual evoked responses.
- Behavioral testing revealed decreased performance in trained monkeys, indicating reduced reinforcer efficacy and impaired attentional set-shifting and motor ability in one subject.
- Neuropathological analysis confirmed T cell infiltration in the brain tissue of all SIV-infected macaques.
Conclusions:
- SIV infection in rhesus macaques induces neurological and behavioral deficits comparable to human neuroAIDS.
- The SIV-macaque model is validated for studying AIDS dementia pathogenesis and evaluating potential therapeutic interventions.