ORIGINAL RESEARCH article

Front. Psychiatry

Sec. Anxiety and Stress Disorders

Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1546737

Age-dependent effects of H2S on post-traumatic stress disorder in adolescent and adult mice

Provisionally accepted
Bing GuBing Gu1Hai Fen ZhaoHai Fen Zhao2Rui YueRui Yue3Qian LuoQian Luo3Shu Wen YuShu Wen Yu3Ting Ting LiTing Ting Li3Yi Jing ZhaoYi Jing Zhao3Liu DexiangLiu Dexiang1,3*Zhen WangZhen Wang3,4*Cyrus SH HoCyrus SH Ho5
  • 1Shandong University, Jinan, China
  • 2Qilu Hospital, Shandong University, Jinan, Shandong Province, China
  • 3School of Basic Medical Sciences, Shandong University, Jinan, Shandong Province, China
  • 4Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong Province, China
  • 5Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

The final, formatted version of the article will be published soon.

Select one of your emails

You have multiple emails registered with Frontiers:

Notify me on publication

Please enter your email address:

If you already have an account, please login

You don't have a Frontiers account ? You can register here

Among people with post-traumatic stress disorder (PTSD), there is an increased prevalence of age-related diseases. However, the biological mechanisms underlying this phenomenon remain incompletely understood. The expression of cystathionine β-synthase (CBS), one of the main enzymes for endogenous hydrogen sulfide (H2S) production in the brain, is age-dependent. In this study, we examined the influence of CBS/H2S on anxiety and depression-like behavior following the inescapable foot shock (IFS) procedure during early adolescence (postnatal days 28-35) or adulthood (postnatal days 63-70). Our results showed that adult PTSD mice exhibited more pronounced decreases in H2S content and CBS expression in the hippocampus, which were associated with anxiety and depression-like behavior compared with adolescent PTSD mice. Administration of exogenous H2S significantly improved anxiety and depression-like behavior, mitigated synaptic plasticity deficits, and activated the CREB/BDNF signaling pathway in the hippocampus of adolescent PTSD mice. In addition, we found that high dose H2S could improve anxiety and depression-like behavior, mitigate synaptic plasticity deficits, and activate the CREB/BDNF signaling pathway, as well as increase H2S levels in the hippocampus. In contrast, injection of CBS antibody in the hippocampus of adult mice increased anxiety and depressive-like behavior. These results suggest that CBS/ H2S modulates PTSD-like behaviors in an age-dependent manner and may promote synaptic plasticity through activation of the CREB/BDNF pathway in the hippocampus of mice after IFS exposure.

Keywords: Post-traumatic stress disorder, H2S, CBS, inevitable foot shock, Hippocampus

Received: 13 Jan 2025; Accepted: 30 Apr 2025.

Copyright: © 2025 Gu, Zhao, Yue, Luo, Yu, Li, Zhao, Dexiang, Wang and Ho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Liu Dexiang, Shandong University, Jinan, China
Zhen Wang, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, Shandong Province, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material