mPFC GABAergic transmission mediated the role of BDNF signaling in cognitive impairment but not anxiety induced by adolescent social stress

doi:10.1016/j.neuropharm.2020.108412

PSYCH OpenIR

	mPFC GABAergic transmission mediated the role of BDNF signaling in cognitive impairment but not anxiety induced by adolescent social stress
	Xu, Hang 1; Wang, Jiesi 1; Jing, Haiyang 1,2; Ellenbroek, Bart 3; Shao, Feng 4; Wang, Weiwen 1,2
通讯作者	Wang, Weiwen(wangww@psych.ac.cn)
摘要	Depression with comorbid anxiety or cognitive symptoms can vary in terms of symptoms, pathophysiology and antidepressant efficacy, but the underlying neurobiological mechanisms remain to be elucidated. Previous studies from our group and others have shown that as a classic animal model of depression, adolescent social stress (ASS) could stably induce a variety of emotional and cognitive alterations in adult animals, and accompanied by transcriptional decrease in brain-derived neurotrophic factor (BDNF) total and promoter IV levels in the medial prefrontal cortex (mPFC). The present study further identified the GABAergic synaptic and molecular changes downstream of BDNF signaling impairment in the mPFC and roles in various behavioral phenotypes induced by ASS. We found that ASS induced a set of emotional and cognitive symptoms, including decreased social interest, impaired cognitive function, and increased anxiety-like behavior, as well as decreased GABAergic transmission in the mPFC. The specific deletion of BDNF promoter IV directly caused impairments in social interest, cognitive function, and inhibition of GABAergic transmission, but no changes in anxiety-like behavior. Acute microinjections of tropomyosin-related kinase B (TrkB) agonists into the mPFC and chronic antidepressant treatment ameliorated the changes in social behavior and cognition, as well as the reduction in GABAergic synaptic transmission in the mPFC, but not anxiety in previously stressed adult mice. These results suggest that the downstream GABAergic transmission of BDNF signaling in the mPFC involved in depression with comorbid cognitive dysfunction induced by ASS and can be used as a therapeutic target for the treatment of cognitive dysfunction in depression. This article is part of the special issue on Stress, Addiction and Plasticity.
关键词	Adolescent social stress Depression Cognitive dysfunction Anxiety Brain-derived neurotrophic factor (BDNF) GABAergic transmission
	2021-02-15
语种	英语
DOI	10.1016/j.neuropharm.2020.108412
发表期刊	NEUROPHARMACOLOGY
ISSN	0028-3908
卷号	184 页码:10
收录类别	SCI
资助项目	National Natural science Foundation of China[31771217] ; National Natural science Foundation of China[81471122] ; Ministry of Science and Technology of China[2017YFE0126500] ; Special Research Assistant program of Chinese Academy of science[E0ZZ0210] ; Key Laboratory of Mental Health, Institute of Psychology, CAS
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS关键词	DEPRESSION ; INTERNEURONS ; BEHAVIOR ; TRKB ; TRANSCRIPTION ; NEURONS ; IMPACT ; COMORBIDITY ; ACTIVATION ; EXPRESSION
WOS研究方向	Neurosciences & Neurology ; Pharmacology & Pharmacy
WOS类目	Neurosciences ; Pharmacology & Pharmacy
WOS记录号	WOS:000614900500008
资助机构	National Natural science Foundation of China ; Ministry of Science and Technology of China ; Special Research Assistant program of Chinese Academy of science ; Key Laboratory of Mental Health, Institute of Psychology, CAS
引用统计
文献类型	期刊论文
条目标识符	https://ir.psych.ac.cn/handle/311026/38585
通讯作者	Wang, Weiwen
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, Dept Psychol, Beijing, Peoples R China 3.Victoria Univ Wellington, Sch Psychol, Wellington 6012, New Zealand 4.Peking Univ, Sch Psychol & Cognit Sci, Beijing Key Lab Behav & Mental Hlth, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Xu, Hang,Wang, Jiesi,Jing, Haiyang,et al. mPFC GABAergic transmission mediated the role of BDNF signaling in cognitive impairment but not anxiety induced by adolescent social stress[J]. NEUROPHARMACOLOGY,2021,184:10.
APA	Xu, Hang,Wang, Jiesi,Jing, Haiyang,Ellenbroek, Bart,Shao, Feng,&Wang, Weiwen.(2021).mPFC GABAergic transmission mediated the role of BDNF signaling in cognitive impairment but not anxiety induced by adolescent social stress.NEUROPHARMACOLOGY,184,10.
MLA	Xu, Hang,et al."mPFC GABAergic transmission mediated the role of BDNF signaling in cognitive impairment but not anxiety induced by adolescent social stress".NEUROPHARMACOLOGY 184(2021):10.