Increase in cortical procholecystokinin gene expression induced by a meningo-cortical injury: studies on the involvement of the "immediate early gene" c-fos.

In rat cortex, a meningo-cortical injury causes complex changes in the expression of the "immediate early" genes c-fos and c-jun as well as the neuropeptide gene procholecystokinin. Within 1 h, mRNA levels of c-fos and c-jun are enhanced. Three hours later they have returned to control values. Twenty-four hours after the injury, there is a second rise in the level of c-fos-mRNA, which is accompanied by an increase in procholecystokinin-mRNA. In the present study, it was investigated whether these events are causally connected. When MK-801 (1.5 mg/kg), an ion-channel blocker, was injected 7 and 19 h after the injury, i.e. after the first rise in expression of both "immediate early" genes, it prevented the later increase in procholecystokinin-mRNA. When given 30 min prior to the injury, MK-801 (4 mg/kg) prevented the increased expression of c-fos but did not affect the later rise in procholecystokinin-mRNA. In a third experiment the cortex injury was performed in a manner which did not increase procholecystokinin-mRNA in frontal cortex. Nevertheless, expression of the c-fos gene was enhanced when determined 24 h after the operation. It is concluded that the injury-induced rise in the expression of the procholecystokinin gene is not connected with the changes in c-fos-mRNA.