Elevated brain monoamine oxidase activity in SIV- and HIV-associated neurological disease.

TitleElevated brain monoamine oxidase activity in SIV- and HIV-associated neurological disease.
Publication TypeJournal Article
Year of Publication2014
AuthorsMeulendyke, KA, Ubaida-Mohien, C, Drewes, JL, Liao, Z, Gama, L, Witwer, KW, Graham, DR, M Zink, C
JournalJ Infect Dis
Volume210
Issue6
Pagination904-12
Date Published2014 Sep 15
ISSN1537-6613
KeywordsAdult, AIDS Dementia Complex, Animals, Brain, Brain Chemistry, Corpus Striatum, 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.

DOI10.1093/infdis/jiu194
Alternate JournalJ. Infect. Dis.
PubMed ID24688074
PubMed Central IDPMC4156136
Grant List5U01MH083500 / MH / NIMH NIH HHS / United States
N01MH32002 / MH / NIMH NIH HHS / United States
NS38841 / NS / NINDS NIH HHS / United States
P01 MH070306 / MH / NIMH NIH HHS / United States
P40 OD013117 / OD / NIH HHS / United States
P40 OD013117 / OD / NIH HHS / United States
R01 MH069116 / MH / NIMH NIH HHS / United States
R01 MH085554 / MH / NIMH NIH HHS / United States
R01 MH087233 / MH / NIMH NIH HHS / United States
R24MH068855 / MH / NIMH NIH HHS / United States
R24MH59724 / MH / NIMH NIH HHS / United States
R24MH59745 / MH / NIMH NIH HHS / United States
R24NS45491 / NS / NINDS NIH HHS / United States
U01MH083501 / MH / NIMH NIH HHS / United States
U01MH083506 / MH / NIMH NIH HHS / United States
U01MH083507 / MH / NIMH NIH HHS / United States
U01MH083545 / MH / NIMH NIH HHS / United States
U24 MH100928 / MH / NIMH NIH HHS / United States
U24 MH100929 / MH / NIMH NIH HHS / United States