Differential temporal patterns of expression of immediate early genes in cerebral cortex induced by intracerebral excitotoxin injection: sensitivity to dexamethasone and MK-801.
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.
Collaço-Moraes
Y
Y
Department of Biochemistry, Charing Cross and Westminster Medical School, London, U.K.
De Belleroche
J
J
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D015870:Gene Expression; D017781:Genes, Immediate-Early / Q000235:genetics*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D016291:Dizocilpine Maleate; D003907:Dexamethasone