Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid.
Huntington's disease (HD) is an autosomal dominant neurological disorder characterized by progressive chorea, cognitive impairment and emotional disturbance. The disease usually occurs in midlife and symptoms progress inexorably to mental and physical incapacitation. It has been postulated that an excitotoxin is involved in the pathogenesis of HD. Schwarcz and colleagues have shown that quinolinic acid (QA) can produce axon-sparing lesions similar to those observed in HD. The lesions result in a depletion of neurotransmitters contained within striatal spiny neurones, for example gamma-aminobutyric acid (GABA), while dopamine is unaffected. Recently, we and others have demonstrated that in HD striatum there is a paradoxical 3-5-fold increase in both somatostatin and neuropeptide Y which is attributable to selective preservation of a subclass of striatal aspiny neurones in which these peptides are co-localized. In the present study we demonstrate that lesions due to quinolinic acid closely resemble those of HD as they result in marked depletions of both GABA and substance P, with selective sparing of somatostatin/neuropeptide Y neurones. Lesions produced by kainic acid (KA), ibotenic acid (IA) and N-methyl-D-aspartate (MeAsp) were unlike those produced by QA, as they affected all cell types without sparing somatostatin/neuropeptide Y neurones. These results suggest that QA or a similar compound could be responsible for neuronal degeneration in HD.
M F
MF
Beal
N W
NW
Kowall
D W
DW
Ellison
M F
MF
Mazurek
K J
KJ
Swartz
J B
JB
Martin
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009478:Neuropeptide Y; D011725:Pyridines / Q000633:toxicity; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D014018:Tissue Distribution; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D011725:Pyridines; D011805:Quinolinic Acids; D013373:Substance P; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D017378:Quinolinic Acid