Increased concentrations of the neurotoxin 3-hydroxykynurenine in the frontal cortex of HIV-1-positive patients.

Abstract

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.

• Authors: A M Sardar, J E Bell, G P Reynolds
• Journal: Journal of neurochemistry (J Neurochem) Vol. 64 Issue 2 Pg. 932-5 (Feb 1995) ISSN: 0022-3042 [Print] England
• PMID: 7830088 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neurotoxins
• 3-hydroxykynurenine
• Kynurenine

Topics

• AIDS Dementia Complex (metabolism)
• Adult
• Female
• Frontal Lobe (metabolism)
• HIV Seropositivity (metabolism)
• HIV-1 (immunology)
• Humans
• Kynurenine (analogs & derivatives, metabolism)
• Male
• Neurotoxins (metabolism)
• Osmolar Concentration
• Reference Values