Differential temporal patterns of expression of immediate early genes in cerebral cortex induced by intracerebral excitotoxin injection: sensitivity to dexamethasone and MK-801

Abstract

A number of conditions associated with persistent excitation such as electrically and chemically-induced seizures cause a rapid increase in the expression of immediate early genes (IEG) such as c-fos. In this study the time-course of induction of c-jun, jun-B and zif 268 mRNA by kainate was characterized in rat cerebral cortex and compared to that of c-fos mRNA induction. Unilateral injection of kainate into the nucleus basalis caused a significant induction of c-jun mRNA in cerebral cortex from 4 hr which was maximal at 8 hr, being 3 times greater in ipsilateral cortex than in control cortex. This pattern was also shown for jun-B and was similar, but of small magnitude, to that obtained with c-fos mRNA, with a maximal increase at 8 hr, whilst the maximal induction of zif-268 mRNA preceded these responses occurring at 4 hr. A marked difference was seen in duration in the c-jun induction which was maintained at a high level for at least 24 hr. Treatment of animals with MK-801 (within 30 min of injection of kainate) or dexamethasone (2-30 mg/kg) at the time of kainate injection significantly attenuated the response. The induction of c-fos mRNA by kainate injection was most sensitive to dexamethasone (2 mg/kg), whereas a higher dose (30 mg/kg) was required to attenuate the induction of zif-268 mRNA. These results show that a time-dependent and co-ordinated induction of c-fos, c-jun, jun-B and zif-268 mRNA in cerebral cortex occurs in response to the persistent excitation caused by excitotoxin injection which is mediated by glutamate and shows a differential sensitivity to dexamethasone.