{"title":"Mild traumatic brain injury increases vulnerability to post-traumatic stress disorder in rats and the possible role of hippocampal DNA methylation.","authors":"Yujie Niu, Zhibiao Cai, Junkai Cheng, Jie Zhou, Xiaodong Qu, Changdong Li, Zhongjing Zhang, Shenghao Zhang, Yaqiang Nan, Qifeng Tang, Lei Zhang, Yelu Hao","doi":"10.3389/fnbeh.2025.1539028","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Clinical studies have established that patients with mild traumatic brain injury (mTBI) are at an increased risk for developing post-traumatic stress disorder (PTSD), suggesting that mTBI increases vulnerability to subsequent PTSD onset. However, preclinical animal studies investigating this link remain scarce, and the specific biological mechanism through which mTBI increases vulnerability to PTSD is largely unknown.</p><p><strong>Methods: </strong>In this study, we modeled mTBI in rats using a mild, closed-head, weight-drop injury, followed 72 h later by exposure to single prolonged stress (SPS) to simulate PTSD. Then, we investigated the impact of mTBI on subsequent PTSD development by observing the behaviors of rats in a series of validated behavioral tests and further explored the possible role of hippocampal DNA methylation.</p><p><strong>Results: </strong>We found that, compared with rats in the PTSD-only group, those in the mTBI + PTSD group exhibited higher anxiety levels, higher depression levels, and impaired spatial learning and memory as determined in the open field test, the forced swimming test, and the Morris water maze test, respectively. Rats in the mTBI + PTSD group also exhibited higher hippocampal DNMT3b protein expression compared with those in the PTSD group.</p><p><strong>Conclusion: </strong>In conclusion, our results demonstrated that mTBI increases vulnerability to PTSD in rats, possibly through alterations in hippocampal DNA methylation patterns.</p>","PeriodicalId":12368,"journal":{"name":"Frontiers in Behavioral Neuroscience","volume":"19 ","pages":"1539028"},"PeriodicalIF":2.6000,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911326/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Behavioral Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fnbeh.2025.1539028","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Clinical studies have established that patients with mild traumatic brain injury (mTBI) are at an increased risk for developing post-traumatic stress disorder (PTSD), suggesting that mTBI increases vulnerability to subsequent PTSD onset. However, preclinical animal studies investigating this link remain scarce, and the specific biological mechanism through which mTBI increases vulnerability to PTSD is largely unknown.
Methods: In this study, we modeled mTBI in rats using a mild, closed-head, weight-drop injury, followed 72 h later by exposure to single prolonged stress (SPS) to simulate PTSD. Then, we investigated the impact of mTBI on subsequent PTSD development by observing the behaviors of rats in a series of validated behavioral tests and further explored the possible role of hippocampal DNA methylation.
Results: We found that, compared with rats in the PTSD-only group, those in the mTBI + PTSD group exhibited higher anxiety levels, higher depression levels, and impaired spatial learning and memory as determined in the open field test, the forced swimming test, and the Morris water maze test, respectively. Rats in the mTBI + PTSD group also exhibited higher hippocampal DNMT3b protein expression compared with those in the PTSD group.
Conclusion: In conclusion, our results demonstrated that mTBI increases vulnerability to PTSD in rats, possibly through alterations in hippocampal DNA methylation patterns.
期刊介绍:
Frontiers in Behavioral Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the neural mechanisms underlying behavior. Field Chief Editor Nuno Sousa at the Instituto de Pesquisa em Ciências da Vida e da Saúde (ICVS) is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
This journal publishes major insights into the neural mechanisms of animal and human behavior, and welcomes articles studying the interplay between behavior and its neurobiological basis at all levels: from molecular biology and genetics, to morphological, biochemical, neurochemical, electrophysiological, neuroendocrine, pharmacological, and neuroimaging studies.