The Effect of Electroconvulsive Therapy on Hippocampal Endoplasmic Reticulum Stress in a Rat Model of Depression

The mechanisms underlying the effectiveness of electroconvulsive therapy (ECT), one of the most effective treatments for depression, are still unknown. While the increasing endoplasmic reticulum (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 change after repeated ECT in rats in the chronic unpredictable mild stress (CUMS) model.

Rats were divided into 4 groups. Two groups were included in the experimental group, where the CUMS model was applied for 21 days. Then, the experimental ECT model was applied to 2 groups, one experimental and 1 control group, for 21 days. Weight changes results were evaluated at the end of the 21st and 42nd day. In the final step, 3 prominent ER stress-related proteins (Grp-78, Xbp1, and Atf-4) were measured by western blot in the removed hippocampus.

We found that rats administered CUMS exhibited depression-like behavioral responses such as weight loss. In CUMS-treated rats (group 3), Grp-78 levels increased, ATF4 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 (group 2). When ECT was applied to rats undergoing the CUMS model, Grp-78 and Xbp1 levels decreased, while Atf-4 levels did not change (group 4).

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.