Neuroscience findings in AIDS: a review of research sponsored by the National Institute of Mental Health.
1. The human immunodeficiency virus (HIV-1) infects cells in both the immune system and the brain, but these effects are not independent. 2. Research funded by the National Institute of Mental Health (NIMH) has been directed at identifying some of the mechanisms by which HIV-1 infects the brain, produces pathology, causes behavioral changes, and alters immune responses. 3. HIV-1-associated peptides have been shown to produce immunological changes without active virus present and there is also evidence that neurological damage may result not from direct viral action, by via excitotoxin production. 4. Rhesus macaque monkeys infected with simian immunodeficiency virus (SIV) are proving to be a useful model of the neurological and behavioral changes identified in human AIDS patients; behavioral changes observed in monkeys are similar to those seen in humans infected with HIV-1. 5. Studies examining the relationship between the brain and immune system are identifying the role that the macrophage cytokine interleukin-1 may play in suppressing T-lymphocyte activity by two pathways, both mediated by corticotropin releasing factor (CRF). 6. One pathway involves the pituitary-adrenal axis and release of glucocorticoids while the other involves direct interaction with the sympathetic noradrenergic nervous system, which has been shown to innervate T-lymphocytes in the spleen and thymus. 7. These observations are relevant because macrophages infected with HIV-1 infiltrate the brain and may release substances that damage the brain. 8. Stress may affect these pathways via the CRF-mediated release of glucocorticoids; a model of stress has also demonstrated that stress can suppress the cellular immune response.
Pequegnat
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Office of AIDS Programs, NIMH, Rockville, MD.
Garrick
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NA
Stover
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E
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000503:physiopathology*; D000818:Animals; D006801:Humans; D009315:National Institute of Mental Health (U.S.); D009422:Nervous System Diseases / Q000209:etiology / Q000503:physiopathology*; D012109:Research Support as Topic; D014481:United States