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mPFC GABAergic transmission mediated the role of BDNF signaling in cognitive impairment but not anxiety induced by adolescent social stress
Xu, Hang1; Wang, Jiesi1; Jing, Haiyang1,2; Ellenbroek, Bart3; Shao, Feng4; Wang, Weiwen1,2
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
DOI10.1016/j.neuropharm.2020.108412
发表期刊NEUROPHARMACOLOGY
ISSN0028-3908
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
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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
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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.
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