Association Between Stress-Induced Weight Loss and Autophagy-Related Gene Expression in the Hippocampus and Midbrain of Depression Model Mice.

AIM: Recent studies have implicated autophagy in both weight regulation and depression. This study aimed to investigate the relationship between stress-induced weight loss and autophagy-related gene expression in a mouse model of depression.

METHOD: Male C57BL/6 mice were subjected to a chronic immobilization stress (CIS) protocol for 14 days to induce depressive-like behavior. Body weight was measured before and after the CIS, and depressive-like behavior was assessed using the tail suspension test (TST). The expression levels of autophagy-related genes (Atg5, Atg7, Atg12, Becn1, Mmp9, Fkbp5, and Map1lc3b) in the hippocampus and midbrain were evaluated using reverse transcription-quantitative PCR (RT-qPCR). Serum cortisol levels were also measured.

RESULTS

The CIS resulted in significant weight loss and increased immobility time in the TST, indicating depressive-like behavior. Serum cortisol levels were not different between CIS-depression model and control mice. In the hippocampus, the expression levels of Fkbp5, Mmp9, and Map1lc3b were significantly higher in CIS-depression model mice than in control mice. In the midbrain, the expression levels of Fkbp5 and Mmp9 were significantly higher in CIS-depression model mice than in control mice. Increased autophagy-related gene expressions in CIS-depression model mice were consistent with the previous studies in the postmortem brains of patients with depression. A significant negative correlation was also found between Fkbp5 mRNA expression in the hippocampus and the weight change ratio before and after the CIS.

CONCLUSION

The findings suggest that enhanced autophagy may be related to the pathology of depression and that Fkbp5, an autophagy regulator, mediates stress-induced weight loss.