title: Elevated cerebrospinal fluid quinolinic acid levels are associated with region-specific cerebral volume loss in HIV infection.
abstract: Neuronal injury, dendritic loss and brain atrophy are frequent complications of infection with human immunodeficiency virus (HIV) type 1. Activated brain macrophages and microglia can release quinolinic acid, a neurotoxin and NMDA (N-methyl-D-aspartate) receptor agonist, which we hypothesize contributes to neuronal injury and cerebral volume loss. In the present cross-sectional study of 94 HIV-1-infected patients, elevated CSF quinolinic acid concentrations correlated with worsening brain atrophy, quantified by MRI, in regions vulnerable to excitotoxic injury (the striatum and limbic cortex) but not in regions relatively resistant to excitotoxicity (the non-limbic cortex, thalamus and white matter). Increased CSF quinolinic acid concentrations also correlated with higher CSF HIV-1 RNA levels. In support of the specificity of these associations, blood levels of quinolinic acid were unrelated to striatal and limbic volumes, and CSF levels of beta(2)-microglobulin, a non-specific and non-excitotoxic marker of immune activation, were unrelated to regional brain volume loss. These results are consistent with the hypothesis that quinolinic acid accumulation in brain tissue contributes to atrophy in vulnerable brain regions in HIV infection and that virus replication is a significant driver of local quinolinic acid biosynthesis.
authors.affiliation: Laboratory of Neurotoxicology, National Institute of Mental Health, Bethesda, Maryland, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Heyes
authors.forename: R J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: L
authors.initials: L
authors.lastname: Ryan
authors.forename: M E
authors.initials: ME
authors.lastname: Childers
authors.forename: I
authors.initials: I
authors.lastname: Grant
authors.forename: T
authors.initials: T
authors.lastname: Wolfson
authors.forename: S
authors.initials: S
authors.lastname: Archibald
authors.forename: T L
authors.initials: TL
authors.lastname: Jernigan
mesh_terms: D000328:Adult; D001284:Atrophy / Q000150:complications / Q000175:diagnosis* / Q000209:etiology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology*; D015331:Cohort Studies; D003342:Corpus Striatum / Q000473:pathology; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000134:cerebrospinal fluid* / Q000150:complications / Q000821:virology; D006679:HIV Seropositivity / Q000150:complications / Q000175:diagnosis; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008032:Limbic System / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D017378:Quinolinic Acid / Q000097:blood / Q000134:cerebrospinal fluid*; D012367:RNA, Viral / Q000134:cerebrospinal fluid; D014779:Virus Replication; D001613:beta 2-Microglobulin / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; D012367:RNA, Viral; D001613:beta 2-Microglobulin; D017378:Quinolinic Acid