{"title":"早期生活压力会导致雄性大鼠内侧前额叶皮层中 CB1R 和 FAAH 的表达减少以及表观遗传学变化。","authors":"Arijana Demaili, Anna Portugalov, Mouna Maroun, Irit Akirav, Katharina Braun, Jörg Bock","doi":"10.3389/fncel.2024.1474992","DOIUrl":null,"url":null,"abstract":"<p><p>Several studies in both animal models and in humans have provided substantial evidence that early life stress (ELS) induces long-term changes in behavior and brain function, making it a significant risk factor in the aetiology of various mental disorders, including anxiety and depression. In this study, we tested the hypothesis that ELS in male rats (i) leads to increased anxiety and depressive-like symptoms; and (ii) that these behavioral changes are associated with functional alterations in the endocannabinoid system of the medial prefrontal cortex (mPFC). We further assessed whether the predicted changes in the gene expression of two key components of the endocannabinoid system, cannabinoid receptor 1 (CB1R) and the fatty acid amide hydrolase (FAAH), are regulated by epigenetic mechanisms. Behavioral profiling revealed that the proportion of behaviorally affected animals was increased in ELS exposed male rats compared to control animals, specifically showing symptoms of anhedonia and impaired social behavior. On the molecular level we observed a decrease in CB1R and FAAH mRNA expression in the mPFC of adult ELS exposed animals. These gene expression changes were accompanied by reduced global histone 3 acetylation in the mPFC, while no significant changes in DNA methylation and no significant changes of histone-acetylation at the promoter regions of the analyzed genes were detected. Taken together, our data provide evidence that ELS induces a long-term reduction of CB1R and FAAH expression in the mPFC of adult male rats, which may partially contribute to the ELS-induced changes in adult socio-emotional behavior.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534599/pdf/","citationCount":"0","resultStr":"{\"title\":\"Early life stress induces decreased expression of CB1R and FAAH and epigenetic changes in the medial prefrontal cortex of male rats.\",\"authors\":\"Arijana Demaili, Anna Portugalov, Mouna Maroun, Irit Akirav, Katharina Braun, Jörg Bock\",\"doi\":\"10.3389/fncel.2024.1474992\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Several studies in both animal models and in humans have provided substantial evidence that early life stress (ELS) induces long-term changes in behavior and brain function, making it a significant risk factor in the aetiology of various mental disorders, including anxiety and depression. In this study, we tested the hypothesis that ELS in male rats (i) leads to increased anxiety and depressive-like symptoms; and (ii) that these behavioral changes are associated with functional alterations in the endocannabinoid system of the medial prefrontal cortex (mPFC). We further assessed whether the predicted changes in the gene expression of two key components of the endocannabinoid system, cannabinoid receptor 1 (CB1R) and the fatty acid amide hydrolase (FAAH), are regulated by epigenetic mechanisms. Behavioral profiling revealed that the proportion of behaviorally affected animals was increased in ELS exposed male rats compared to control animals, specifically showing symptoms of anhedonia and impaired social behavior. On the molecular level we observed a decrease in CB1R and FAAH mRNA expression in the mPFC of adult ELS exposed animals. These gene expression changes were accompanied by reduced global histone 3 acetylation in the mPFC, while no significant changes in DNA methylation and no significant changes of histone-acetylation at the promoter regions of the analyzed genes were detected. 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引用次数: 0
摘要
对动物模型和人类的多项研究提供了大量证据,证明早期生活压力(ELS)会诱发行为和大脑功能的长期变化,使其成为焦虑症和抑郁症等各种精神疾病发病的重要风险因素。在这项研究中,我们检验了以下假设:雄性大鼠的 ELS(i)会导致焦虑和抑郁症状的增加;(ii)这些行为变化与内侧前额叶皮层(mPFC)的内源性大麻素系统的功能改变有关。我们进一步评估了内源性大麻素系统的两个关键组成部分--大麻素受体 1(CB1R)和脂肪酸酰胺水解酶(FAAH)的基因表达的预期变化是否受到表观遗传机制的调控。行为分析表明,与对照组动物相比,暴露于 ELS 的雄性大鼠中受行为影响的动物比例增加,具体表现为失神症状和社交行为受损。在分子水平上,我们观察到暴露于 ELS 的成年动物的 mPFC 中 CB1R 和 FAAH mRNA 表达减少。伴随这些基因表达变化的是 mPFC 中全局组蛋白 3 乙酰化的减少,而 DNA 甲基化没有发生显著变化,分析基因启动子区域的组蛋白乙酰化也没有发生显著变化。总之,我们的数据提供了证据,证明 ELS 会诱导成年雄性大鼠 mPFC 中 CB1R 和 FAAH 表达的长期减少,这可能是 ELS 诱导成年社会情感行为变化的部分原因。
Early life stress induces decreased expression of CB1R and FAAH and epigenetic changes in the medial prefrontal cortex of male rats.
Several studies in both animal models and in humans have provided substantial evidence that early life stress (ELS) induces long-term changes in behavior and brain function, making it a significant risk factor in the aetiology of various mental disorders, including anxiety and depression. In this study, we tested the hypothesis that ELS in male rats (i) leads to increased anxiety and depressive-like symptoms; and (ii) that these behavioral changes are associated with functional alterations in the endocannabinoid system of the medial prefrontal cortex (mPFC). We further assessed whether the predicted changes in the gene expression of two key components of the endocannabinoid system, cannabinoid receptor 1 (CB1R) and the fatty acid amide hydrolase (FAAH), are regulated by epigenetic mechanisms. Behavioral profiling revealed that the proportion of behaviorally affected animals was increased in ELS exposed male rats compared to control animals, specifically showing symptoms of anhedonia and impaired social behavior. On the molecular level we observed a decrease in CB1R and FAAH mRNA expression in the mPFC of adult ELS exposed animals. These gene expression changes were accompanied by reduced global histone 3 acetylation in the mPFC, while no significant changes in DNA methylation and no significant changes of histone-acetylation at the promoter regions of the analyzed genes were detected. Taken together, our data provide evidence that ELS induces a long-term reduction of CB1R and FAAH expression in the mPFC of adult male rats, which may partially contribute to the ELS-induced changes in adult socio-emotional behavior.
期刊介绍:
Frontiers in Cellular Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the cellular mechanisms underlying cell function in the nervous system across all species. Specialty Chief Editors Egidio D‘Angelo at the University of Pavia and Christian Hansel at the University of Chicago are supported by an outstanding Editorial Board of international researchers. 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.