Effect of Hypothermia on the Expression of C-fos and C-jun Protooncogenes in a transient Global Cerebral Ischemic Model of Gerbil

Park, Sung Chan; Park, Hae Kwan; Cho, Kyung Keun; Park, Young Sup; Kim, Dal Soo; Choi, Chang Rak

Abstract

Increased release of excitatory neurotransmitters leading to activation of signal transduction has been noted after cerebral ischemia. One of the biochemical events in the signaling processes is an alteration of gene expression, that is, increased expression of immediate early genes(IEGs) such as the protooncogenes, c-fos and c-jun. Recent studies have shown that hypothermia has a beneficial protective effect on hippocampal neuronal loss during or after cerebral ischemia. In this study, we investigated the expressions of c-fos and c-jun by immunohistochemical stain at the hippocampal CA1, CA3 and parietal cortex(PC) along the changes of body temperature in a transient global cerebral ischemia model of gerbil in order to check the effect of hypothermia The experimental groups were divided into control(36~36.5 degrees C), normothermic(36~36.5degrees C), hypothermic(32~33 degrees C) and hyperthermic groups(38~39 degrees C)and a transient global cerebral ischemia was made by clipping of both common carotid arteries for 10 minutes, followed by reperfusion for 120 minutes. The results were as follows; 1) In all ischemic groups, the expressions of c-fos and c-jun were increased with the control group. The expression of c-fos was markedly enhanced and that of c-jun was also enhanced in a similar pattern, but lower in count, than that of c-fos. 2) The expression of c-fos at the hippocampal CA1 was enhanced significantly in all three ischemic groups compared with the control group(P<0.01). At the hippocampal CA3 and parietal cortex(PC), the expression was enhanced significantly in the normothermic and hypothermic groups(P<0.01), but not in the hyperthermic group compared with the control group. 3) The expression of c-jun at the hippocampal CA3 was enhanced sighificantly in the hypothermic group compared with all other groups(P<0.01) but there was no significant change in hippocampal CA1 and PC. 4) In the aspect of location in each experimental group, the expressions of both protooncogenes were increased in CA1