Environmental enrichment modulates HPA axis reprogramming in adult male rats exposed to early adolescent stress
Environmental enrichment modulates HPA axis reprogramming in adult male rats exposed to early adolescent stress
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DOI：
10.1016/j.neures.2021.04.007
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发表时间：
2021-09-14
影响因子：
2.9
通讯作者：
Yan, Can
中科院分区：
文献类型：
--
作者：
Fan, Zhixin;Chen, Jie;Yan, Can
成年后暴露于早期应激事件会增加创伤后应激障碍(PTSD)的易感性，而下丘脑-垂体-肾上腺(HPA)轴在其中起着至关重要的作用。研究发现，环境丰富(EE)可以减轻早期逆境的有害后果。然而，与HPA相关的机制仍不清楚。本研究采用单次持续应激(SPS)范式，探讨青春期早期应激对行为、HPA轴活性以及下丘脑和海马区糖皮质激素受体(GR)、盐皮质激素受体(MR)、促肾上腺皮质激素释放激素受体1(CRF1R)和CRF2R的表达水平的长期影响。同时检测EE干预的保护作用。我们发现，暴露于青春期应激的成年雄性大鼠表现出运动活动减少，类焦虑行为增加，情景恐惧记忆增强，基础血浆ACTH水平升高，HPA负反馈抑制增强，地塞米松抑制试验(DST)中血浆ACTH水平下降表明。此外，EE可使应激大鼠的行为异常恢复正常，并增强HPA的负反馈，可能是通过下调海马区和下丘脑区GR的表达。这些发现表明，EE可以改善青少年应激诱导的PTSD样行为和HPA轴的异常重编程，降低成年后患PTSD的风险。(C)2021年提交人。由Elsevier B.V.出版。这是CC BY-NC-ND许可证(http://creativecommons.org/licenses/by-nc-nd/4.0/).下的一篇开放获取文章
Exposure to early stressful events increases susceptibility to post-traumatic stress disorder (PTSD) in adulthood, in which the hypothalamic-pituitary-adrenal (HPA) axis plays a crucial role. Studies have found that environmental enrichment (EE) mitigates the detrimental outcomes of early adversity. How -ever, the HPA-related mechanism remains unclear. In this study, we used the single prolonged stress (SPS) paradigm to explore the long-term effects of early adolescent stress on behavior, HPA axis activ-ity, as well as expression levels of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), corticotropin-releasing hormone receptor 1 (CRF1R) and CRF2R in the hypothalamus and hippocam-pus. Meanwhile, the protective effects of EE intervention were examined. We found that adult male rats exposed to adolescent stress showed reduced locomotor activity, increased anxiety-like behaviors, enhanced contextual fear memory, elevated basal plasma ACTH levels, and enhanced HPA negative feed-back inhibition, as indicated by decreased plasma ACTH levels in the dexamethasone suppression test (DST). Furthermore, EE normalized the behavioral abnormalities and enhanced HPA negative feedback in stressed rats, possibly through down-regulating GR expression in the hippocampus and hypothalamus. These findings suggested that EE could ameliorate adolescent stress-induced PTSD-like behaviors and aberrant reprogramming of the HPA axis, reducing the risk of developing PTSD in adulthood. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).