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. 2025 May;398(5):5785-5796.
doi: 10.1007/s00210-024-03637-z. Epub 2024 Nov 29.

Tauroursodeoxycholic acid mitigates depression-like behavior and hippocampal neuronal damage in a corticosterone model of female mice

Wei Shen #  1 , Zikang Li #  1 , Yanlin Tao  1 , Houyuan Zhou  1 , Hui Wu  1 , Hailian Shi  1 , Fei Huang  2 , Xiaojun Wu  3
Affiliations

Tauroursodeoxycholic acid mitigates depression-like behavior and hippocampal neuronal damage in a corticosterone model of female mice

Wei Shen et al. Naunyn Schmiedebergs Arch Pharmacol. 2025 May.

Abstract

Depression, a complex mental disorder influenced by both psychological and physiological factors, predominantly affects females. Studies have indicated that elevated levels of cortisol/corticosterone (CORT) under stress conditions can lead to hippocampal neuronal damage, thereby contributing to depression. Tauroursodeoxycholic acid (TUDCA), a bile acid, possesses anti-apoptotic, antioxidant, and anti-inflammatory properties. This study aimed to investigate the protective mechanism of TUDCA against CORT-induced neuromolecular and behavioral phenotypes of depression in female mice, providing theoretical support for its use in treating female depression. The antidepressant effects of TUDCA were evaluated through a series of behavioral tests, measurement of serum neurotransmitter levels, Nissl staining of the hippocampal CA3 region, and assessment of hippocampal proteins. Behavioral results demonstrated that TUDCA exhibited antidepressant effects, as evidenced by increased sucrose preference and locomotor activity, as well as reduced immobility time in depressed mice. Furthermore, TUDCA ameliorated neurotransmitter imbalances. Nissl staining revealed that TUDCA reduced neuronal damage in depressed mice, while Western blotting results indicated that TUDCA activated the hippocampal BDNF/TrkB/CREB pathway and regulated the expression of GR-related proteins. These findings suggested that TUDCA exerted neuroprotective effects in CORT-induced neuronal damage in female depressed mice. The mechanism appeared to be related to the activation of the BDNF/TrkB/CREB signaling pathway and the modulation of GR-related protein expression.

Keywords: Corticosterone; Depression; Female; Hippocampal neurons; Tauroursodeoxycholic acid.

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Conflict of interest statement

Declarations: During the preparation of this work, the authors used ChatGPT 3.5 to improve the language. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication. Competing interests: The authors declare no competing interests.

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