DIFFERENTIAL EXPRESSION OF THE ASTROCYTIC ENZYMES 3-HYDROXYANTHRANILIC ACID OXYGENASE, KYNURENINE AMINOTRANSFERASE AND GLUTAMINE-SYNTHETASEIN SEIZURE-PRONE AND NONEPILEPTIC MICE

Previous investigations in seizure-prone mice have suggested that an a bnormally elevated production of the astrocyte-derived neuroexcitant, quinolinic acid (QUIN), plays a role in seizure susceptibility. In ord er to evaluate further the role of QUIN metabolism in genetic murine s eizure models, the activities of its bio synthetic enzyme 3-hydroxyant hranilic acid oxygenase (3HAO), and of two other astrocytic enzymes, k ynurenine aminotransferase (KAT) and glutamine synthetase (GS), were m easured in the brains of seizure-prone EL and DBA/2 mice and two non-e pileptic strains (BALB/c and Swiss-Webster). 3HAO activity was found t o be markedly higher in both EL and DBA/2 mice than in the non-epilept ic strains in all brain regions examined. The activity of 3HAO was not modified by the tossing procedure employed to promote seizures in EL mice. While some strain differences were noted in the activities of KA T and GS, these enzymes did not distinguish seizure-prone from the non -epileptic mice. In order to delineate better the relationship between glial activation and 3HAO, KAT and GS, further studies were performed in the ibotenate-lesioned hippocampus. In mice (but not in rats), the activity of 3HAO was selectively increased in gliotic tissue. These d ata demonstrate substantial species and strain differences in astrogli al enzymes and in their response to brain injury. The observation of w idespread abnormally high 3HAO activity in two distinct seizure-prone mouse strains strengthens the hypothesis that enhanced production of Q UIN contributes to seizure susceptibility in mice.