title: Oxidative mitochondrial DNA damage in peripheral blood mononuclear cells is associated with reduced volumes of hippocampus and subcortical gray matter in chronically HIV-infected patients.
abstract: Cross-sectional relationships were examined between regional brain volumes and mitochondrial DNA (mtDNA) 8-hydroxy-2-deoxyguanosine (8-oxo-dG) in peripheral blood mononuclear cells (PBMCs) of 47 HIV patients [mean age 51years; 81% with HIV RNA ≤50copies/mL] on combination antiretroviral therapy. The gene-specific DNA damage and repair assay measured mtDNA 8-oxo-dG break frequency. Magnetic resonance imaging was performed at 3T. Higher mtDNA 8-oxo-dG was associated with lateral ventricular enlargement and with decreased volumes of hippocampus, pallidum, and total subcortical gray matter, suggesting the involvement of systemic mitochondrial-specific oxidative stress in chronic HIV-related structural brain changes and cognitive difficulties. Clarification of the mechanism may provide potential therapeutic targets.
authors.affiliation: Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, Honolulu HI 96813, United States. Electronic address: kalpana@hawaii.edu.
authors.forename: Kalpana J
authors.initials: KJ
authors.lastname: Kallianpur
authors.affiliation: Department of Cell and Molecular Biology, John A. Burns School of Medicine, Honolulu HI 96813, United States.
authors.forename: Mariana
authors.initials: M
authors.lastname: Gerschenson
authors.affiliation: Department of Tropical Medicine, John A. Burns School of Medicine, Honolulu HI 96813, United States.
authors.forename: Brooks I
authors.initials: BI
authors.lastname: Mitchell
authors.affiliation: Department of Cell and Molecular Biology, John A. Burns School of Medicine, Honolulu HI 96813, United States.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: LiButti
authors.affiliation: Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, Honolulu HI 96813, United States.
authors.forename: Tracie M
authors.initials: TM
authors.lastname: Umaki
authors.affiliation: Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, Honolulu HI 96813, United States; Department of Tropical Medicine, John A. Burns School of Medicine, Honolulu HI 96813, United States.
authors.forename: Lishomwa C
authors.initials: LC
authors.lastname: Ndhlovu
authors.affiliation: Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, Honolulu HI 96813, United States; Straub Clinics and Hospital, Honolulu HI 96813, United States.
authors.forename: Beau K
authors.initials: BK
authors.lastname: Nakamoto
authors.affiliation: Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, Honolulu HI 96813, United States.
authors.forename: Dominic C
authors.initials: DC
authors.lastname: Chow
authors.affiliation: Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, Honolulu HI 96813, United States.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Shikuma
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D001284:Atrophy / Q000000981:diagnostic imaging / Q000473:pathology*; D003430:Cross-Sectional Studies; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000737:chemistry*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D015658:HIV Infections / Q000150:complications*; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000633:toxicity
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine
keywords: Atrophy; Brain; Neuroinflammation; Oxidative stress; Pallidum; ROS