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

BackgroundAmong 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.MethodsThe expression of cystathionine β-synthase (CBS), one of the main enzymes f...

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Main Authors: Bing Gu, Ting Li, Haifen Zhao, Rui Yue, Qian Luo, Shuwen Yu, Tingting Li, Yijing Zhao, Dexiang Liu, Zhen Wang, Cyrus S. H. Ho
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Psychiatry
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Online Access:https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1546737/full
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author Bing Gu
Ting Li
Haifen Zhao
Rui Yue
Qian Luo
Shuwen Yu
Tingting Li
Yijing Zhao
Dexiang Liu
Zhen Wang
Cyrus S. H. Ho
author_facet Bing Gu
Ting Li
Haifen Zhao
Rui Yue
Qian Luo
Shuwen Yu
Tingting Li
Yijing Zhao
Dexiang Liu
Zhen Wang
Cyrus S. H. Ho
author_sort Bing Gu
collection DOAJ
description BackgroundAmong 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.MethodsThe 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).ResultsOur 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. ConclusionThese 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.
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spelling doaj-art-bdb4cc0eb436486a8097c6f7009e57452025-08-20T03:09:51ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402025-06-011610.3389/fpsyt.2025.15467371546737Age-dependent effects of H2S on post-traumatic stress disorder in adolescent and adult miceBing Gu0Ting Li1Haifen Zhao2Rui Yue3Qian Luo4Shuwen Yu5Tingting Li6Yijing Zhao7Dexiang Liu8Zhen Wang9Cyrus S. H. Ho10Department of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Psychiatry, Liaocheng People's Hospital, Liaocheng, Shandong, ChinaUrology of Qilu Hospital, Shandong University, Jinan, Shandong, ChinaDepartment of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeBackgroundAmong 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.MethodsThe 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).ResultsOur 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. ConclusionThese 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.https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1546737/fullpost-traumatic stress disorderH2SCBSinevitable foot shockhippocampus
spellingShingle Bing Gu
Ting Li
Haifen Zhao
Rui Yue
Qian Luo
Shuwen Yu
Tingting Li
Yijing Zhao
Dexiang Liu
Zhen Wang
Cyrus S. H. Ho
Age-dependent effects of H2S on post-traumatic stress disorder in adolescent and adult mice
Frontiers in Psychiatry
post-traumatic stress disorder
H2S
CBS
inevitable foot shock
hippocampus
title Age-dependent effects of H2S on post-traumatic stress disorder in adolescent and adult mice
title_full Age-dependent effects of H2S on post-traumatic stress disorder in adolescent and adult mice
title_fullStr Age-dependent effects of H2S on post-traumatic stress disorder in adolescent and adult mice
title_full_unstemmed Age-dependent effects of H2S on post-traumatic stress disorder in adolescent and adult mice
title_short Age-dependent effects of H2S on post-traumatic stress disorder in adolescent and adult mice
title_sort age dependent effects of h2s on post traumatic stress disorder in adolescent and adult mice
topic post-traumatic stress disorder
H2S
CBS
inevitable foot shock
hippocampus
url https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1546737/full
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