Work

Exercise Exerts Antidepressant Effects via Endoplasmic Reticulum Stress Modulation: Molecular Mechanisms and Research Progress

Year: 2026

Type: article

Abstract: Abnormal activation of endoplasmic reticulum stress (ERS) is an important driving factor for the occurrence and development of depression. As a safe and effective non-drug intervention, exercise plays an important role in improving depression-like behavior. This paper systematically reviews the core role of ERS-mediated neuronal apoptosis, inflammatory response, calcium homeostasis imbalance and autophagy abnormalities in depression and focuses on the molecular mechanism of exercise to improve depression by regulating ERS and its downstream signals. Existing evidence shows that exercise can exert antidepressant effects through multi-level remodeling of ERS-related signaling networks, including inhibiting UPR-related apoptosis, inhibiting microglial pro-inflammatory polarization, regulating MAMs-mediated calcium-mitochondrial interaction, and restoring autophagy activity (LC3-II, Beclin-1). Although the above findings provide a new potential perspective for explaining the antidepressant effect of exercise, its precise intervention application is still limited by the lack of population research, unclear selection of exercise types and large differences in exercise intensity. This article aims to review and analyze the mechanism of endoplasmic reticulum stress in the improvement of depression by exercise, in order to provide a new theoretical reference for the prevention and treatment of depression.

Source: Biology

DOI: 10.3390/biology15110836