Elevated brain monoamine oxidase activity in SIV- and HIV-associated neurological disease.
Title | Elevated brain monoamine oxidase activity in SIV- and HIV-associated neurological disease. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Meulendyke, KA, Ubaida-Mohien, C, Drewes, JL, Liao, Z, Gama, L, Witwer, KW, Graham, DR, M Zink, C |
Journal | J Infect Dis |
Volume | 210 |
Issue | 6 |
Pagination | 904-12 |
Date Published | 2014 Sep 15 |
ISSN | 1537-6613 |
Keywords | Adult, AIDS Dementia Complex, Animals, Brain, Brain Chemistry, Corpus Striatum, External, Female, Gene Expression Profiling, Glutathione, Humans, Macaca nemestrina, Male, Middle Aged, Monoamine Oxidase, Oxidative Stress, Real-Time Polymerase Chain Reaction, Simian Acquired Immunodeficiency Syndrome, Viral Load |
Abstract | We recently demonstrated direct evidence of increased monoamine oxidase (MAO) activity in the brain of a simian immunodeficiency virus (SIV) model of human immunodeficiency virus (HIV)-associated central nervous system (CNS) disease, consistent with previously reported dopamine deficits in both SIV and HIV infection. In this study, we explored potential mechanisms behind this elevated activity. MAO B messenger RNA was highest in macaques with the most severe SIV-associated CNS lesions and was positively correlated with levels of CD68 and GFAP transcripts in the striatum. MAO B messenger RNA also correlated with viral loads in the CNS of SIV-infected macaques and with oxidative stress. Furthermore, in humans, striatal MAO activity was elevated in individuals with HIV encephalitis, compared with activity in HIV-seronegative controls. These data suggest that the neuroinflammation and oxidative stress caused by SIV infection in the CNS may provide the impetus for increased transcription of MAO B and that MAO, and more broadly, oxidative stress, have significant potential as therapeutic targets in CNS disease due to HIV. |
DOI | 10.1093/infdis/jiu194 |
Alternate Journal | J Infect Dis |
PubMed ID | 24688074 |
PubMed Central ID | PMC4156136 |
Grant List | U24 MH100929 / MH / NIMH NIH HHS / United States U01 MH083507 / MH / NIMH NIH HHS / United States R24 MH059724 / MH / NIMH NIH HHS / United States R01 MH069116 / MH / NIMH NIH HHS / United States U01 MH083500 / MH / NIMH NIH HHS / United States R01 MH087233 / MH / NIMH NIH HHS / United States R24 NS045491 / NS / NINDS NIH HHS / United States N01MH32002 / MH / NIMH NIH HHS / United States R01 MH085554 / MH / NIMH NIH HHS / United States U24 MH100928 / MH / NIMH NIH HHS / United States 5U01MH083500 / MH / NIMH NIH HHS / United States R24MH068855 / MH / NIMH NIH HHS / United States R24MH59724 / MH / NIMH NIH HHS / United States R24 MH059745 / MH / NIMH NIH HHS / United States R24MH59745 / MH / NIMH NIH HHS / United States R24NS45491 / NS / NINDS NIH HHS / United States P01 MH070306 / MH / NIMH NIH HHS / United States R24 NS038841 / NS / NINDS NIH HHS / United States U01MH083501 / MH / NIMH NIH HHS / United States U01 MH083501 / MH / NIMH NIH HHS / United States U01MH083506 / MH / NIMH NIH HHS / United States U01 MH083545 / MH / NIMH NIH HHS / United States U01 MH083506 / MH / NIMH NIH HHS / United States U01MH083507 / MH / NIMH NIH HHS / United States P40 OD013117 / OD / NIH HHS / United States R24 MH068855 / MH / NIMH NIH HHS / United States U01MH083545 / MH / NIMH NIH HHS / United States NS38841 / NS / NINDS NIH HHS / United States |