Increased quinolinic acid metabolism following neuronal degeneration in the rat hippocampus.
The excitotoxic brain metabolite quinolinic acid (QUIN) has been hypothetically linked to the pathogenesis of seizure disorders and other neurodegenerative events affecting the hippocampal formation. Its biosynthetic enzyme, 3-hydroxyanthranilic acid oxygenase (3-HAO) and its catabolic enzyme, quinolinic acid phosphoribosyltransferase (QPRT), can be used as markers for the cellular localization of the brain's QUIN system. Measured between 2 days and 2 months following intrahippocampal ibotenic acid injections, the activities of both enzymes increased at the lesion site due to the synthesis of new enzyme protein. The time course of the increase in 3-HAO activity coincided with that of the known astrocytic proliferation following excitotoxic insults. It is less obvious if the elevation in QPRT activity, too, is related to an increase in the number of reactive glial cells. No changes in the activity of hippocampal 3-HAO or QPRT were noted 7 or 60 days after cholinergic deafferentation by fornix-fimbria transection nor were any changes observed in the contralateral hippocampus at any time-point following the ibotenate lesion. These data raise the possibility that a feed-forward mechanism, resulting in ever increasing amounts of QUIN in the brain, may be operant in situations of progressive hippocampal nerve cell loss.
D000818:Animals; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009410:Nerve Degeneration; D010088:Oxidoreductases / Q000378:metabolism; D010430:Pentosyltransferases / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating)
D011725:Pyridines; D011805:Quinolinic Acids; D010088:Oxidoreductases; C026382:3-hydroxyanthranilic acid oxidase; D010430:Pentosyltransferases; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating); D017378:Quinolinic Acid