Effect of electroconvulsive therapy on hippocampal endoplasmic reticulum stress in Rat Depression Model

Aim: The mechanisms underlying the effectiveness of electroconvulsive therapy (ECT), one of the most effective treatments for depression, are still unknown. While the increasing ER stress in depression can retrieve with pharmacological agents, ECT's effectiveness has not been examined yet. In this study, we tested how hippocampal ER stress parameters changed after the repeated ECT in the rats depression model. Material and Method: Rats were divided into 4 groups. An experimental depression model was tried to be created for 2 groups in the experimental group using the chronic unpredictable mild stress model (CUMS) for 21 days. Then, the experimental ECT model was applied to two groups, one experimental and one control group, for 21 days. Weight changes and Forced Swimming Test (FST) results were evaluated at the end of the 21st and 42nd day. In the final step, three prominent ER stress-related proteins (Grp-78, Xbp1, and Atf-4) were measured by Western Blot in the removed hippocampus. Results: We found that rats administered CUMS exhibited depression-like behavioral responses such as weight loss, although the increased immobility time expected in FST did not fully occur. In CUMS-treated rats, Grp-78 levels increased, Atf-4 levels did not change, and Xbp1 levels decreased. While ECT increased Grp-78 levels in normal rats, it did not change Atf-4 levels and reduced Xbp1 levels. In rats treated with depression model, Grp-78 levels, which increased with ECT, decreased, Atf-4 levels did not change, and Xbp1 levels decreased. Conclusion: These findings show that increased ER stress may play a role in the pathophysiology of depression and that this increase can be reversed with ECT treatment. These findings need to be confirmed by clinical studies in humans. Key words: Depression, ECT, Endoplasmic Reticulum Stress