Neurocytotoxity of quinolinic acid in human brain cultures.
Quinolinic acid (QUIN) is a tryptophan metabolite which has been found to be an excitotoxin in rats, although its toxicity in humans is unknown. QUIN has been implicated in the pathogenesis of AIDS dementia complex. This study examined the effect of QUIN on human fetal brain tissue in vitro. After at least 14 days in vitro, QUIN was added to the cultures in the feeding medium, and lactate dehydrogenase (LDH) efflux at 20 h and neuronal morphology were used as a measure of neuronal injury. LDH levels in media from cultures exposed to QUIN concentrations of 5 and 10 mM were consistently elevated compared to controls. Overall, LDH levels in media from cultures exposed to lower QUIN concentrations did not differ significantly from controls. These data are comparable to animal in vitro studies, and support the hypothesis that QUIN is toxic to human central nervous system neurons and further strengthen its potential role in the pathogenesis of AIDS dementia complex.
Kerr
S J
SJ
Department of HIV Medicine, St Vincent's Hospital, Darlinghurst, NSW, Australia.
Armati
P J
PJ
Brew
B J
BJ
D015526:AIDS Dementia Complex / Q000378:metabolism / Q000821:virology; D001253:Astrocytes / Q000166:cytology / Q000821:virology; D001921:Brain / Q000166:cytology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005333:Fetus / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D009498:Neurotoxins / Q000633:toxicity*; D017378:Quinolinic Acid / Q000633:toxicity*
D009498:Neurotoxins; D007770:L-Lactate Dehydrogenase; D017378:Quinolinic Acid