Isoflurane produces antidepressant effects inducing BDNF-TrkB signaling in CUMS mice

doi:10.1007/s00213-019-05287-z

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	Isoflurane produces antidepressant effects inducing BDNF-TrkB signaling in CUMS mice
	Zhang, Sha-Sha 1; Tian, Yu-Hua 1; Jin, Song-Jun 2; Wang, Wen-Cheng 3; Zhao, Jing-Xin 1; Si, Xiao-Ming 1; Zhang, Li 4; Xu, Hong 5; Jin, Jing-Yu 1
	2019-11-01
发表期刊	PSYCHOPHARMACOLOGY
ISSN	0033-3158
卷号	236 期号:11 页码:3301-3315
通讯作者	Jin, Jing-Yu([email protected])
摘要	Rationale The volatile anesthetic isoflurane is suggested to produce a rapid and robust antidepressive effect in preliminary clinical trials. Recently, isoflurane was found to activate the tropomyosin receptor kinase B (TrkB) signaling which is the underlying mechanism of the rapid antidepressant ketamine. Objective Our study investigated the effect of isoflurane anesthesia on chronic unpredictable mild stressed (CUMS) model in mice and verified the role of brain-derived neurotrophic factor (BDNF)/TrkB/ the mammalian target of rapamycin (mTOR) signaling in the antidepressant effect of isoflurane. Methods We employed the CUMS model of depression to assess the rapid antidepressant effect of isoflurane by the forced swimming test (FST), the sucrose preference test (SPT), and the novelty suppressed feeding test (NSFT). The protein expression of BDNF and TrkB/protein kinase B (PKB or Akt)/mTOR was determined through Western blot. The dendritic spine density in the hippocampus and medial prefrontal cortex (PFC) was measured by the Golgi staining. Results A brief burst-suppressing isoflurane anesthesia rapidly reversed the behavioral deficits caused by CUMS procedure, normalized the expression of BDNF and further activated the TrkB signaling pathway in CUMS-induced stressed mice in both prefrontal cortex (PFC) and hippocampus (HC). All of those behavioral and proteomic effects were blocked by K252a, a selective receptor inhibitor of TrkB. Isoflurane significantly promoted the formation of dendritic spines in both medial prefrontal cortex (mPFC), CA1, CA3, and DG of the hippocampus. Conclusion Our study indicates that isoflurane exerts a rapid antidepressant-like effect in CUMS depression animal model, and the activation of BDNF/TrkB signaling pathway plays an indispensable role in the biological and behavioral antidepressant effects of isoflurane. A single exposure to isoflurane could repair synaptic damage caused by chronic stimulation.
关键词	Isoflurane Rapid antidepressant activity Chronic unpredictable mild stressed Brain-derived neurotrophic factor Tropomyosin receptor kinase B Dendritic spine density
DOI	10.1007/s00213-019-05287-z
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[31272397]; Natural Science Foundation of Shandong Province[ZR2011CM041]; Qingdao Postdoctoral Application Research Project
WOS研究方向	Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
WOS类目	Neurosciences ; Pharmacology & Pharmacy ; Psychiatry
WOS记录号	WOS:000494045800021
出版者	SPRINGER
引用统计	被引频次：36[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/165044
专题	实验海洋生物学重点实验室
通讯作者	Jin, Jing-Yu
作者单位	1.Qingdao Univ, Sch Pharm, Dept Pharmacol, Dengzhou Rd, Qingdao 266021, Shandong, Peoples R China 2.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao 266071, Shandong, Peoples R China 3.Qingdao Municipal Ctr Dis Control & Prevent, Dept Immunizat Program, Qingdao 266033, Shandong, Peoples R China 4.Qingdao Univ, Expt Ctr Undergrad Pharm, Sch Pharm, Qingdao 266021, Shandong, Peoples R China 5.Qingdao Univ, Affiliated Hosp, Sch Stomatol, Dept Orthodont, Qingdao 266003, Shandong, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Sha-Sha,Tian, Yu-Hua,Jin, Song-Jun,et al. Isoflurane produces antidepressant effects inducing BDNF-TrkB signaling in CUMS mice[J]. PSYCHOPHARMACOLOGY,2019,236(11):3301-3315.
APA	Zhang, Sha-Sha.,Tian, Yu-Hua.,Jin, Song-Jun.,Wang, Wen-Cheng.,Zhao, Jing-Xin.,...&Jin, Jing-Yu.(2019).Isoflurane produces antidepressant effects inducing BDNF-TrkB signaling in CUMS mice.PSYCHOPHARMACOLOGY,236(11),3301-3315.
MLA	Zhang, Sha-Sha,et al."Isoflurane produces antidepressant effects inducing BDNF-TrkB signaling in CUMS mice".PSYCHOPHARMACOLOGY 236.11(2019):3301-3315.

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