Predictable Chronic Mild Stress during Adolescence Promotes Fear Memory Extinction in Adulthood

Abstract Early-life stress in adolescence has a long-lasting influence on brain function in adulthood, and it is mostly recognized as a predisposing factor for mental illnesses, such as anxiety and posttraumatic stress disorder. Previous studies also indicated that adolescent predictable chronic mil...

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Autores principales:	Jia-Hui Deng, Wei Yan, Ying Han, Chen Chen, Shi-Qiu Meng, Cheng-Yu Sun, Ling-Zhi Xu, Yan-Xue Xue, Xue-Jiao Gao, Na Chen, Fei-Long Zhang, Yu-Mei Wang, Jie Shi, Lin Lu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c86312766b7f4392b182b00fe540b36b
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spelling	oai:doaj.org-article:c86312766b7f4392b182b00fe540b36b2021-12-02T15:06:05ZPredictable Chronic Mild Stress during Adolescence Promotes Fear Memory Extinction in Adulthood10.1038/s41598-017-08017-72045-2322https://doaj.org/article/c86312766b7f4392b182b00fe540b36b2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08017-7https://doaj.org/toc/2045-2322Abstract Early-life stress in adolescence has a long-lasting influence on brain function in adulthood, and it is mostly recognized as a predisposing factor for mental illnesses, such as anxiety and posttraumatic stress disorder. Previous studies also indicated that adolescent predictable chronic mild stress (PCMS) in early life promotes resilience to depression- and anxiety-like behaviors in adulthood. However, the role of PCMS in associated memory process is still unclear. In the present study, we found that adolescent PCMS facilitated extinction and inhibited fear response in reinstatement and spontaneous recovery tests in adult rats, and this effect was still present 1 week later. PCMS in adolescence increased the activity of brain-derived neurotrophic factor (BDNF)-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in infralimbic cortex (IL) but not prelimbic cortex in adulthood. Intra-IL infusion of BDNF antibody and the ERK1/2 inhibitor U0126 reversed PCMS-induced enhancement of fear extinction. Moreover, we found that PCMS decreased DNA methylation of the Bdnf gene at exons IV and VI and elevated the mRNA levels of Bdnf in the IL. Our findings indicate that adolescent PCMS exposure promotes fear memory extinction in adulthood, which reevaluates the traditional notion of adolescent stress.Jia-Hui DengWei YanYing HanChen ChenShi-Qiu MengCheng-Yu SunLing-Zhi XuYan-Xue XueXue-Jiao GaoNa ChenFei-Long ZhangYu-Mei WangJie ShiLin LuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jia-Hui Deng Wei Yan Ying Han Chen Chen Shi-Qiu Meng Cheng-Yu Sun Ling-Zhi Xu Yan-Xue Xue Xue-Jiao Gao Na Chen Fei-Long Zhang Yu-Mei Wang Jie Shi Lin Lu Predictable Chronic Mild Stress during Adolescence Promotes Fear Memory Extinction in Adulthood
description	Abstract Early-life stress in adolescence has a long-lasting influence on brain function in adulthood, and it is mostly recognized as a predisposing factor for mental illnesses, such as anxiety and posttraumatic stress disorder. Previous studies also indicated that adolescent predictable chronic mild stress (PCMS) in early life promotes resilience to depression- and anxiety-like behaviors in adulthood. However, the role of PCMS in associated memory process is still unclear. In the present study, we found that adolescent PCMS facilitated extinction and inhibited fear response in reinstatement and spontaneous recovery tests in adult rats, and this effect was still present 1 week later. PCMS in adolescence increased the activity of brain-derived neurotrophic factor (BDNF)-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in infralimbic cortex (IL) but not prelimbic cortex in adulthood. Intra-IL infusion of BDNF antibody and the ERK1/2 inhibitor U0126 reversed PCMS-induced enhancement of fear extinction. Moreover, we found that PCMS decreased DNA methylation of the Bdnf gene at exons IV and VI and elevated the mRNA levels of Bdnf in the IL. Our findings indicate that adolescent PCMS exposure promotes fear memory extinction in adulthood, which reevaluates the traditional notion of adolescent stress.
format	article
author	Jia-Hui Deng Wei Yan Ying Han Chen Chen Shi-Qiu Meng Cheng-Yu Sun Ling-Zhi Xu Yan-Xue Xue Xue-Jiao Gao Na Chen Fei-Long Zhang Yu-Mei Wang Jie Shi Lin Lu
author_facet	Jia-Hui Deng Wei Yan Ying Han Chen Chen Shi-Qiu Meng Cheng-Yu Sun Ling-Zhi Xu Yan-Xue Xue Xue-Jiao Gao Na Chen Fei-Long Zhang Yu-Mei Wang Jie Shi Lin Lu
author_sort	Jia-Hui Deng
title	Predictable Chronic Mild Stress during Adolescence Promotes Fear Memory Extinction in Adulthood
title_short	Predictable Chronic Mild Stress during Adolescence Promotes Fear Memory Extinction in Adulthood
title_full	Predictable Chronic Mild Stress during Adolescence Promotes Fear Memory Extinction in Adulthood
title_fullStr	Predictable Chronic Mild Stress during Adolescence Promotes Fear Memory Extinction in Adulthood
title_full_unstemmed	Predictable Chronic Mild Stress during Adolescence Promotes Fear Memory Extinction in Adulthood
title_sort	predictable chronic mild stress during adolescence promotes fear memory extinction in adulthood
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c86312766b7f4392b182b00fe540b36b
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Predictable Chronic Mild Stress during Adolescence Promotes Fear Memory Extinction in Adulthood

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