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Effects of adolescent social stress and antidepressant treatment on cognitive inflexibility and Bdnf epigenetic modifications in the mPFC of adult mice
Xu, Hang1,2; Wang, Jiesi1,2; Zhang, Ke1,2; Zhao, Mei1,2; Ellenbroek, Bart4; Shao, Feng3; Wang, Weiwen1,2; F. Shao; W. Wang
2018-02-01
发表期刊PSYCHONEUROENDOCRINOLOGY
通讯作者邮箱shaof@pku.edu.cn ; wangww@psych.ac.cn
ISSN0306-4530
文章类型Article
卷号88页码:92-101
产权排序1
摘要

Adolescent social stress (ASS) can increase susceptibility to depression in adulthood. However, the underlying psychological and neural mechanisms remain unclear. Cortically mediated cognitive dysfunctions are increasingly recognized as an independent and important risk factor of depression. Using social defeat stress, a classical animal model of depression, our previous studies found that mice subjected to this form of stress during early adolescence displayed cognitive inflexibility (CI) in adulthood. This change was accompanied by a down-regulation of Bdnf gene expression in the medial prefrontal cortex (mPFC); this gene encodes a key molecule involved in depression and antidepressant action. In the present paper, we identified epigenetic modification of Bdnf as a possible mechanism underlying the behavioral and molecular changes. ASS induced a set of depressive phenotypes, including increased social avoidance and CI, as well as reduced levels of total Bdnf and isoform IV but not isoform I or VI transcripts in the mPFC. In parallel with changes in Bdnf gene expression, previously stressed adult mice showed increased levels of dimethylation of histone H3 at lysine K9 (H3K9me2) immediately downstream of the Bdnf 11, promoter. On the other hand, no differences were found in trimethylation of histone H3 at lysine K4 (H3K4me3) or in acetylation of histone H3 at lysine K9 (H3K9ac) or at K4 (H3K4ac) in the Bdnf IV promoter. Likewise, no alterations were found in DNA methylation of the Bdnf IV promoter. Additionally, treatment with the chronic antidepressant tranylcypromine reversed Bdnf epigenetic changes and related gene transcription while also reversing CI, but not social avoidance, in previously stressed adult mice. These results suggest that epigenetic changes to the Bdnf gene in the mPFC after adolescent social adversity may be involved in the regulation of cognitive dysfunction in depression and antidepressant action in adulthood.

关键词Adolescent Social stress Cognitive inflexibility Brain-derived neurotrophic factor (BDNF) Epigenetic mechanism
DOI10.1016/j.psyneuen.2017.11.013
收录类别SCI
语种英语
项目资助者National Natural Science Foundation of China(81471122 ; Chinese Academy of Sciences(KJZD-EW-L04) ; CAS Key Laboratory of Mental Health, Institute of Psychology ; 31470988)
WOS研究方向Endocrinology & Metabolism ; Neurosciences & Neurology ; Psychiatry
WOS类目Endocrinology & Metabolism ; Neurosciences ; Psychiatry
WOS记录号WOS:000426236000011
WOS标题词Science & Technology ; Life Sciences & Biomedicine
关键词[WOS]HISTONE LYSINE METHYLATION ; NEUROTROPHIC FACTOR ; DNA METHYLATION ; PSYCHIATRIC-DISORDERS ; MAJOR DEPRESSION ; PRENATAL STRESS ; ANIMAL-MODELS ; HUMAN GENOME ; MOUSE MODEL ; BRAIN
引用统计
文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/26032
专题中国科学院心理健康重点实验室
通讯作者F. Shao; W. Wang
作者单位1.Inst Psychol, CAS Key Lab Mental Hlth, 16 Lincui Rd, Beijing 100101, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Peking Univ, Beijing Key Lab Behav & Mental Hlth, Sch Psychol & Cognit Sci, Beijing, Peoples R China
4.Victoria Univ Wellington, Sch Psychol, Wellington 6012, New Zealand
推荐引用方式
GB/T 7714
Xu, Hang,Wang, Jiesi,Zhang, Ke,et al. Effects of adolescent social stress and antidepressant treatment on cognitive inflexibility and Bdnf epigenetic modifications in the mPFC of adult mice[J]. PSYCHONEUROENDOCRINOLOGY,2018,88:92-101.
APA Xu, Hang.,Wang, Jiesi.,Zhang, Ke.,Zhao, Mei.,Ellenbroek, Bart.,...&W. Wang.(2018).Effects of adolescent social stress and antidepressant treatment on cognitive inflexibility and Bdnf epigenetic modifications in the mPFC of adult mice.PSYCHONEUROENDOCRINOLOGY,88,92-101.
MLA Xu, Hang,et al."Effects of adolescent social stress and antidepressant treatment on cognitive inflexibility and Bdnf epigenetic modifications in the mPFC of adult mice".PSYCHONEUROENDOCRINOLOGY 88(2018):92-101.
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