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Chronic corticosterone injections induce a decrease of ATP levels and sustained activation of AMP-activated protein
1Laboratory of Pharmaceutical Sciences, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
Abstract:
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.
Insights
Chronic corticosterone exposure in mice caused depression-like behaviors and altered hippocampal energy metabolism. Sustained activation of AMP-activated protein kinase (AMPK) may underlie these effects, despite unchanged adenylate kinase (AK) levels.
Area of Science:
- Neuroscience
- Metabolic Research
- Behavioral Science
Background:
- Chronic corticosterone exposure is linked to hippocampus damage and depression-like behaviors.
- Adenylate kinase (AK) and AMP-activated protein kinase (AMPK) are crucial for neuronal energy metabolism.
- Dysregulation of AK or AMPK systems can impair brain function, particularly in energy-demanding situations.
Purpose of the Study:
- To investigate the impact of chronic corticosterone exposure on hippocampal energy metabolism.
- To examine the roles of AK and AMPK in corticosterone-induced depression-like behaviors in mice.
Main Methods:
- Male C57BL/6N mice received chronic corticosterone injections.
- Hippocampal tissues were analyzed for energy levels, AMP:ATP ratio, and AK1/AMPK protein and mRNA.
- Depression-like behaviors were assessed in the mice.
Main Results:
- Corticosterone injections induced depression-like behavior and decreased hippocampal energy levels.
- A sustained increase in the AMP:ATP ratio was observed in hippocampal tissues.
- While AK1 levels remained unaffected, AMPK showed sustained activation.
Conclusions:
- Sustained activation of AMPK in the hippocampus may be a key mechanism underlying corticosterone-induced depression-like behavior.
- Energy metabolism disturbances, indicated by increased AMP:ATP ratio, are associated with these behavioral changes.
- Further research into AMPK's role could reveal therapeutic targets for depression.
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