Prolonged infusion of quinolinic acid into rat striatum as an excitotoxic model of neurodegenerative disease.
The neurotoxic effects of prolonged exposure of rat striatum to quinolinic acid in vivo was evaluated through assays of neurochemical markers for major neuronal populations. Continuous intrastriatal quinolinic acid infusion for 14 days produced a dose-dependent depletion of striatal choline acetyltransferase (ChAT) activity, glutamic acid decarboxylase (GAD) activity, and somatostatin content. ChAT activity was significantly reduced by quinolinic acid at doses of 90, 270, and 540 nmol/day, while GAD activity and somatostatin content were decreased only at doses of 270 and 540 nmol/day. NADPH-diaphorase histochemistry revealed a loss of striatal NADPH-diaphorase neurons as a result of quinolinic acid infusion at a dose of 270 nmol/day. The neurotoxic lesion induced by prolonged quinolinic acid exposure in vivo can be used as a potential model for studying excitotoxic mechanisms in neurodegenerative disease.
Susel
Z
Z
Experimental Therapeutics Branch, National Institutes of Neurological Disorders and Stroke, Bethesda, MD 20892.
Engber
T M
TM
Kuo
S
S
Chase
T N
TN
D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003292:Convulsants / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006651:Histocytochemistry; D006816:Huntington Disease / Q000503:physiopathology; D007267:Injections; D008297:Male; D008954:Models, Biological; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009410:Nerve Degeneration; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000503:physiopathology; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D003292:Convulsants; D011805:Quinolinic Acids; D009252:NADPH Dehydrogenase; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D017378:Quinolinic Acid