Picolinic acid protects against quinolinic acid-induced depletion of NADPH diaphorase containing neurons in the rat striatum.
Previous studies in our laboratory have demonstrated that focal injections of picolinic acid (PIC) protect the cholinergic neurons of the nucleus basalis magnocellularis (nbm) against quinolinic acid (QUIN)-induced neurotoxicity. The present study was designed to examine the effects of chronic infusions of QUIN and PIC on nicotinamide adenine dinucleotide (NADPH) diaphorase containing neurons of the rat striatum. Using osmotic minipumps, QUIN (6 nmol/h) and PIC (18 nmol/h) were infused alone or in combination to examine the neurotoxic effects of QUIN and the potential anti-neurotoxic action of PIC. Exposure to QUIN for 7 days severely depleted NADPH diaphorase-positive neurons. When co-infused with this neurotoxic dose of QUIN, PIC attenuated the depletion of NADPH diaphorase neurons induced by QUIN. The infusion of PIC alone did not affect the number of these neurons. These results indicate that PIC itself is not neurotoxic and effectively prevents chronic QUIN-induced neurotoxicity in the rat striatum. Since PIC and QUIN are derived from the same metabolic pathway, a balance between endogenous compounds that produce neurotoxicity and those antagonizing these effects may be important in normal neuronal function.
Kalisch
B E
BE
Department of Pharmacology, Queen's University, Kingston, Ont., Canada.
Jhamandas
K
K
Boegman
R J
RJ
Beninger
R J
RJ
D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D002799:Cholinergic Fibers / Q000187:drug effects / Q000201:enzymology*; D007150:Immunohistochemistry; D008297:Male; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase; D010848:Picolinic Acids / Q000494:pharmacology*; D017378:Quinolinic Acid / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009498:Neurotoxins; D010848:Picolinic Acids; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009252:NADPH Dehydrogenase; D017378:Quinolinic Acid