CYCLOHEXIMIDE PREVENTS KAINATE-INDUCED NEURONAL DEATH AND C-FOS EXPRESSION IN ADULT-RAT BRAIN

The present study was directed at evaluating the possible involvement of protein synthesis in excitotoxin-induced neuronal damage and prolon ged expression of the proto-oncogene, c-fos. Kainic acid-induced seizu re activity elicited varying degrees of neuronal damage and cell loss in selectively vulnerable regions of the adult rat limbic system. Pret reatment with cycloheximide, a protein synthesis inhibitor, did not al ter behavioral seizure characteristics, but markedly attenuated damage to susceptible neuronal populations. A prolonged increase in c-fos mR NA was observed by in situ hybridization up to 16 h after the onset of seizures in regions exhibiting neuronal death. Pretreatment with cycl oheximide did not affect the transient induction of c-fos observed in numerous structures, but significantly reduced the prolonged expressio n of c-fos mRNA in kainate-vulnerable regions. Despite producing massi ve seizure activity, systemic kainic acid administration during the ea rly postnatal period did not induce any neuronal death, and did not re sult in prolonged c-fos expression in any brain structures. The develo pmental onset of selective neuronal vulnerability coincided with that of prolonged c-fos expression in susceptible neuronal populations. In adult rats, seizure activity induced by pentylenetetrazole did not pro duce neuronal damage nor did it produce prolonged c-fos expression. Th ese results not only demonstrate that kainate-induced neurotoxicity an d the prolonged expression of c-fos are both prevented by cycloheximid e, but also strengthen the idea that prolonged c-fos expression is a m arker of neuronal death.