DIFFERENTIAL RESPONSE OF CALMODULIN GENES IN THE MOUSE-BRAIN AFTER SYSTEMIC KAINATE ADMINISTRATION

In the central nervous system, many of the effects resulting from an i ncrease in the intracellular levels of calcium are mediated by calmodu lin, a major calcium-binding protein in the mammalian brain. Calmoduli n is expressed by three different genes, namely CaM I, CaM II and CaM III, all of which encode an identical protein. We studied the expressi on of calmodulin in the mouse brain at different times after the admin istration of a convulsant dose of kainate, a potent neuroexcitotoxic a gent. We detected the presence of the different calmodulin messenger R NAs and of the protein itself in brain sections by in situ hybridizati on histochemistry and immunocytochemistry respectively. In addition, w e determined the calmodulin content in brain regions by radioimmunoass ay. Kainate-treated animals did not show areas of neuronal death at th e different times following administration considered. An increase in the hybridization signal for CaM I messenger RNAs was observed from 5 h after kainate administration in the different brain regions tested. In contrast, the CaM II messenger RNA signal decreased gradually to a minimum 24 h after treatment in the hippocampus, while the CaM III mes senger RNA signal was mostly unaffected. Calmodulin immunoreactivity a lso increased in the hippocampus. Nevertheless, we did not detect any significant difference in calmodulin content between brain regions of control and treated animals by radioimmunoassay. Kainate treatment ind uced modifications in the expression of calmodulin at the level of bot h messenger RNAs and protein. The results suggest a differential regul ation of the three calmodulin genes in the adult mouse brain and a pos t-transcriptional or a post-translational regulation of calmodulin exp ression. (C) 1997 IBRO.