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Sub-anesthetic and anesthetic ketamine produce different long-lasting behavioral phenotypes (24 h post-treatment) via inducing different brain derived neurotrophic factor (BDNF) expression level in the hippocampus

文献类型：期刊论文

作者Wu, Chunhui1,2; Wang, Yu3; He, Yang3; Wu, Song2; Xie, Zhifei2; Zhang, Jian2; Shen, Jingshan3; Wang, Zhen3; He, Ling1
刊名NEUROBIOLOGY OF LEARNING AND MEMORY
出版日期2020
卷号167页码:10
关键词Ketamine Sub-anesthetic dose Anesthetic dose Depression Cognition Anxiety
ISSN号1074-7427
DOI10.1016/j.nlm.2019.107136
通讯作者Wang, Zhen(wangzhen@simm.ac.cn) ; He, Ling(heling92@hotmail.com)
英文摘要Clinical and preclinical researches have shown that sub-anesthetic ketamine elicits sustained antidepressant effects for up to 1-2 weeks. Pharmacokinetics studies (t1/2 = 23 min) in mice showed no ketamine residue at 24 h after sub-anesthetic or anesthetic ketamine administration. Therefore, this study aims to reveal the mechanism underlying these different biological functions at 24 h after sub-anesthetic and anesthetic ketamine treatment. First, at the animal behavioral level, we found that sub-anesthetic ketamine induced antidepressant and anxiolytic effects while anesthetic ketamine induced depressive-like phenotypes and cognitive impairment. Second, we examined the correlation between behavior phenotype and protein expression, and found that the Brain-derived neurotrophic factor (BDNF) level is oppositely regulated by sub-anesthetic and anesthetic ketamine. Sub-anesthetic ketamine significantly increased the BDNF level, correlating to antidepressant effects; whereas anesthetic dose reduced BDNF expression in the hippocampus, correlating to depressive-like behaviors, anxiety-like behaviors and cognitive impairment. Third, the antidepressant effects of sub-anesthetic ketamine were prevented by pre-treatment of ANA-12, a Tropomyosin receptor kinase B (TrkB) inhibitor. Thus, we conclude that BDNF may be the key factor underlying antidepressant and anxiolytic effects of sub-anesthetic ketamine at 24 h after treatment. These results may shed light on future studies and the development of long-lasting anti-depressant drugs and therapies.
WOS关键词FORCED SWIMMING TEST ; OXIDATIVE STRESS ; ANTIDEPRESSANT ACTIONS ; TRANSCRIPTION FACTORS ; AMPA RECEPTORS ; ANIMAL-MODELS ; DEPRESSION ; MECHANISMS ; PLASTICITY ; TIME
资助项目Strategic Priority Research Program of Chinese Academy of Sciences, China[XDA12040105] ; Scientific and Technological Innovation Program of Science and Technology Commission of Shanghai Municipality, China[17431900500]
WOS研究方向Behavioral Sciences ; Neurosciences & Neurology ; Psychology
语种英语
WOS记录号WOS:000510109300012
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/281686]  
专题中国科学院上海药物研究所
通讯作者Wang, Zhen; He, Ling
作者单位1.China Pharmaceut Univ, Dept Pharmacol, 24 Tong Jia Xiang, Nanjing 210009, Jiangsu, Peoples R China
2.Topharman Shanghai Co Ltd, Dept Pharmacol, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Wu, Chunhui,Wang, Yu,He, Yang,et al. Sub-anesthetic and anesthetic ketamine produce different long-lasting behavioral phenotypes (24 h post-treatment) via inducing different brain derived neurotrophic factor (BDNF) expression level in the hippocampus[J]. NEUROBIOLOGY OF LEARNING AND MEMORY,2020,167:10.
APA Wu, Chunhui.,Wang, Yu.,He, Yang.,Wu, Song.,Xie, Zhifei.,...&He, Ling.(2020).Sub-anesthetic and anesthetic ketamine produce different long-lasting behavioral phenotypes (24 h post-treatment) via inducing different brain derived neurotrophic factor (BDNF) expression level in the hippocampus.NEUROBIOLOGY OF LEARNING AND MEMORY,167,10.
MLA Wu, Chunhui,et al."Sub-anesthetic and anesthetic ketamine produce different long-lasting behavioral phenotypes (24 h post-treatment) via inducing different brain derived neurotrophic factor (BDNF) expression level in the hippocampus".NEUROBIOLOGY OF LEARNING AND MEMORY 167(2020):10.

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来源：上海药物研究所

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