Date Published:
2014 Sep 15

Publication Type:
Journal Article

Authors:

K.A. Meulendyke
C. Ubaida-Mohien
J.L. Drewes
Z. Liao
L. Gama
K.W. Witwer
D.R. Graham
C. Zink

Secondary:
J Infect Dis

Volume:
210

Pagination:
904-12

Issue:
6

PMID:
24688074

URL:
https://pubmed.ncbi.nlm.nih.gov/24688074

DOI:
10.1093/infdis/jiu194

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:
<p>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.</p>