RAS/PI3K信号转导通路在铝致大鼠LTP损害中的作用

he RAS/PI3K signal transduction pathway appears to be involved in the mechanisms of AMPA receptor trafficking and long-term potentiation (LTP). Our previous study in rats showed that acute aluminum treatment suppressed hippocampal LTP in vivo, and this suppression may be related to the decreased trafficking of AMPA receptor subunits. In the present study, we investigated RAS activity in the rat hippocampus after an acute aluminum exposure, and the antagonism of the aluminum-induced suppression of hippocampal LTP by the RAS activator EGF, and the effects of Al and EGF on PKB activity and the phosphorylation of GluR1 S831 and S845. First, acute aluminum exposure by intracerebroventricular injection with an aluminum-maltolate complex (Al(mal)3) produced a dose-dependent decrease in RAS activity in the rat hippocampus. Second, the alumimun-induced early suppression of hippocampal LTP was antagonized by the RAS activator EGF. Finally, EGF treatment produced changes similar to those observed for LTP on PKB activity as well as the phosphorylation of GluR1 S831 and S845. The results suggest that a RAS→PI3K/PKB→GluR1 S831 and S845 signal transduction pathway may be involved in the inhibition of hippocampal LTP by aluminum exposure in rats. However, the mechanisms underlying this observation need further investigation.