Abnormally high activity of 3-hydroxyanthranilate 3,4-dioxygenase in brain of epilepsy-prone El mice

Abstract

Quinolinic acid (QUI), a structural analogue of neurotransmitters such as l-glutamate and l-aspartate, may act as an ‘excitotoxin’ when it is abundant in the brain. The compound has been causally related to various neurodegenerative disorders, including epilepsy 20. We tested the capacity of the brains of epilepsy-prone El mice to synthesize QUI. The activity of 3-hydroxyanthranilate 3,4-dioxygenase in the cerebral cortex of El mice was about 17 times that of ddY mice, the parent strain of El mice. The activity of this enzyme was undetectable in brains of BALB/cA mice and C3H/HeN mice. In El mice the sexes had comparable enzyme activity. The enzyme activity increased gradually as the animals aged. An injection of endotoxin caused a further increase in the enzyme activity. The enzyme activity in the spleen of El mice did not differ from the of ddY mice, and endotoxin did not affect the enzyme activity in the spleen. No strain-difference was observed in the activity of quinolinate phosphoribosyltransferase, a QUI-degrading enzyme, in the cerebral cortex. These results suggest that an increase in the synthesis of QUI in the brain is involved in the pathogenesis of epileptic seizures in El mice.