Increased concentrations of the neurotoxin 3-hydroxykynurenine in the frontal cortex of HIV-1-positive patients.
Human immunodeficiency virus (HIV)-1-associated dementia is a frequent consequence of HIV infection and is associated with neuronal deficits. Increased concentrations of the kynurenine pathway metabolites 3-hydroxykynurenine (3-HK) and quinolinic acid (QA) may contribute to this neuronal damage. We measured 3-HK concentrations and the activity of its catabolising enzyme, 3-hydroxykynureninase, in postmortem brain tissue from eight controls and 32 HIV-positive patients, including a group that exhibited dementia. 3-HK concentrations were significantly increased (over threefold) in the HIV-positive group when compared with controls. This increase was greater in those patients with dementia, but it was still apparent in the nondemented cases. 3-Hydroxykynureninase activity was significantly increased in the HIV-infected group compared with the control values. The effect was apparent in both nondementia and dementia cases, although the latter showed a slightly greater increase. The 3-HK content increase is thus unrelated to a reduction in activity of this enzyme and is likely to reflect an overall increase in the kynurenic metabolic pathway. Elevated levels of the neurotoxin 3-HK may contribute to the neuronal deficits underlying HIV-associated dementia.
Sardar
A M
AM
Department of Biomedical Science, University of Sheffield, England, UK.
Bell
J E
JE
Reynolds
G P
GP
D015526:AIDS Dementia Complex / Q000378:metabolism; D000328:Adult; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006679:HIV Seropositivity / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D009498:Neurotoxins / Q000378:metabolism*; D009994:Osmolar Concentration; D012016:Reference Values
D009498:Neurotoxins; C005045:3-hydroxykynurenine; D007737:Kynurenine