Chronic corticosterone injections induce a decrease of ATP levels and sustained activation of AMP-activated protein kinase in hippocampal tissues of male mice

Chronic corticosterone injections induce hippocampus tissue damage and depression-like behavior in rodent animals, the cause of which is not known. Nevertheless, increasing evidence shows that adenylate kinase (AK) and AMP-activated protein kinase (AMPK) play a very important role in intracellular energy metabolism and are especially critical for neurons which are known to have very small energy reserves and narrow margin of safety between the energy that can be generated and the energy required for maximum activity. Abnormalities of AK or AMPK system have detrimental effects on neurons or brain function especially at times of increased activity. In this study, we investigated the effects of chronic corticosterone exposure on energy metabolism, as well as AK and AMPK in hippocampal tissues in male C57BL/6N mice. Our results show that chronic corticosterone injection induced depression-like behavior in male mice, significantly decreased the energy levels and caused a sustained increase of AMP:ATP ratio in hippocampal tissues. Interestingly, chronic corticosterone injections did not produce obvious effects on AK1 protein and mRNA levels, but caused a sustained activation of AMPK. The results indicate that sustained AMPK activation might be a mechanism by which chronic corticosterone treatment causes depression-like behavior in male mice.