Increased brain quinolinic acid production in mice infected with a hamster neurotropic measles virus.
In order to examine the status of quinolinic acid (QUIN) metabolism in a model of delayed excitotoxic neurodegeneration, the de novo production of QUIN from 3-hydroxyanthranilic acid was assessed in brain homogenates and brain slices of mice injected with hamster neurotropic measles virus. In the hippocampus, which presents exclusive nerve cell loss in this model, the activity of 3-hydroxyanthranilic acid oxygenase, an astrocytic enzyme responsible for the biosynthesis of QUIN, was increased 3.3-fold by 7 days after virus inoculation. Less dramatic increases were observed in the cerebral cortex and the striatum, while cerebellar enzyme activity was not different from control values. In the same brain homogenates, no changes occurred in the activities of kynurenine aminotransferase, the biosynthetic enzyme of the neuroprotectant kynurenic acid, and of the astrocytic marker glutamine synthetase. At 7 days postinoculation, hippocampal slices from virus-treated animals, when exposed to 3-hydroxyanthranilic acid, produced 18 times more QUIN than slices from control animals. Notably, a significant increase was also seen 3 days postinoculation, i.e., at a time when astrocytes had started to proliferate but prior to the onset of neurodegeneration (Eur. J. Neurosci. 3:66-71, 1991). These data suggest that astrocyte-derived QUIN may play a causative role in the occurrence of hippocampal nerve cell loss in measles virus-infected mice.
Eastman
C L
CL
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228.
Urbańska
E
E
Löve
A
A
Kristensson
K
K
Schwarcz
R
R
D050561:3-Hydroxyanthranilate 3,4-Dioxygenase; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D006224:Cricetinae / Q000382:microbiology; D049308:Dioxygenases; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D066298:In Vitro Techniques; D008190:Lyases; D008457:Measles / Q000378:metabolism* / Q000382:microbiology / Q000523:psychology; D008459:Measles virus / Q000145:classification / Q000502:physiology; D051379:Mice; D009420:Nervous System / Q000382:microbiology / Q000473:pathology; D010105:Oxygenases / Q000378:metabolism; D017378:Quinolinic Acid / Q000378:metabolism*; D000637:Transaminases / Q000378:metabolism
D010105:Oxygenases; D049308:Dioxygenases; D050561:3-Hydroxyanthranilate 3,4-Dioxygenase; D000637:Transaminases; C427605:glutamine - phenylpyruvate transaminase; C021481:kynurenine-oxoglutarate transaminase; D008190:Lyases; D005974:Glutamate-Ammonia Ligase; D017378:Quinolinic Acid