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

Kelly A. Meulendyke, Ceereena Ubaida-Mohien, Julia L. Drewes, Zhaohao Liao, Lucio Gama, Kenneth W. Witwer, David R. Graham, M. Christine Zink

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)904-912
Number of pages9
JournalJournal of Infectious Diseases
Volume210
Issue number6
DOIs
StatePublished - Sep 15 2014

Keywords

  • HIV
  • Monoamine oxidase
  • Neuroinflammation
  • Oxidative stress
  • Reactive oxygen species
  • SIV

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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