Effects of theanine on c-Jun N-terminal kinases and P38 signaling pathways in rat hippocampus after ischemia/reperfusion

Abstract

Objective To discuss the effects of theanine(TH) on c-Jun N-terminal kinases (JNK) and P38 signaling pathways in the hippocampus after brain ischemia/reperfusion(I/R). Methods One hundred and eight adult SD rats (290-310 g) were randomly divided into 3 groups: sham operation group(SH group), I/R group, and TH+I/R group(TH group). Transient general brain ischemia was induced by four-vessel occlusion, and the rats were sacrificed at 2, 6, 12, 24, 48 h and 72 h after reperfusion. Phosphorylated c-Jun N-terminal kinases(p-JNK) and phosphorylated P38(p-P38) in hippocampal CA1 region were detected by immunohistochemistry. Survival and apoptotic neurons in hippocampal CA1 region were counted by histochemistry and TUNEL. Results In comparison with SH group, I/R group showed higher levels of p-JNK and p-P38 in hippocampal CA1 region 2-72 h after reperfusion, and the difference reached maximum at 24 h after reperfusion. Interestingly, TH injection 4 h before ischemia prevented the decrease of p-JNK and p-P38 after I/R, and maintained their levels similar to SH group. Additionally, TH also improved neuronal survival and attenuated neuronal apoptosis in hippocampal CA1 region in response to I/R. Conclusions TH protected hippocampal CA1 neurons against I/R-induced apoptosis by inhibiting the phosphorylation of JNK and P38, and might be a therapeutic approach for brain I/R injury. Key words: Brain; Ischemia/reperfusion injury; Apoptosis; Theanine; c-Jun N-terminal kinases; P38