title: Elevated brain monoamine oxidase activity in SIV- and HIV-associated neurological disease.
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.
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Meulendyke
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Ceereena
authors.initials: C
authors.lastname: Ubaida-Mohien
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Drewes
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Zhaohao
authors.initials: Z
authors.lastname: Liao
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Lucio
authors.initials: L
authors.lastname: Gama
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Witwer
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: David R
authors.initials: DR
authors.lastname: Graham
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: M Christine
authors.initials: MC
authors.lastname: Zink
mesh_terms: D015526:AIDS Dementia Complex / Q000201:enzymology*; D000328:Adult; D000818:Animals; D001921:Brain / Q000201:enzymology*; D001923:Brain Chemistry; D003342:Corpus Striatum / Q000201:enzymology; D005260:Female; D020869:Gene Expression Profiling; D005978:Glutathione / Q000032:analysis; D006801:Humans; D008254:Macaca nemestrina / Q000821:virology; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D018384:Oxidative Stress; D060888:Real-Time Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000201:enzymology*; D019562:Viral Load
chemical_list: D008995:Monoamine Oxidase; D005978:Glutathione
keywords: HIV; SIV; monoamine oxidase; neuroinflammation; oxidative stress; reactive oxygen species