Neonatal exposure to ketamine disrupts developmental synapse unsilencing and predisposes adult mice for stressor-evoked anxiety

doi:10.1016/j.neuropharm.2020.108300

	Neonatal exposure to ketamine disrupts developmental synapse unsilencing and predisposes adult mice for stressor-evoked anxiety
	Zhang, Xiaoyun 1,2; Kong, Yue 1,2,3; He, Guiqin 2; Zhou, Zikai 2,3,4
刊名	NEUROPHARMACOLOGY
	2020-12-01
卷号	180 页码:12
关键词	Stress Anxiety Silent synapse Long-term potentiation Anesthesia
ISSN号	0028-3908
DOI	10.1016/j.neuropharm.2020.108300
通讯作者	Zhang, Xiaoyun(xiaoyun_zhang@seu.edu.cn) ; Zhou, Zikai(zhouzikai@simm.ac.cn)
英文摘要	Accumulating evidence suggests long-lasting impairments in brain development and cognition caused by neonatal exposure to general anesthetics. To date, very little is known about potential abnormal psychiatric manifestations attributable to neonatal anesthesia. In this study, we used ketamine to induce anesthesia in neonatal mice. By applying mild stressors one day before behavioral tests, we found that adult mice exhibit significant anxiety-like behaviors that were indistinguishable at basal level. Recruitment of AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) type glutamate receptors into silent synapses is a prominent cellular process during neonatal neurodevelopment. We found that exposure to ketamine significantly disrupted synapse unsilencing, and impaired the expression of unsilencing-mediated long-term potentiation (LTP). Pharmacologically enhancement of neural activities by AMPAkine drug CX546 [1-(1,4-benzodioxan-6-ylcarbonyl) piperidine] effectively rescued disrupted developmental synapse unsilencing and LTP at neonatal age, and prevented stressor-evoked anxiety-like behaviors in adult mice. Together, our results indicate that neonatal exposure to ketamine may predispose individuals for psychiatric conditions via disrupting synapse unsilencing, and potentiation of neural activities during the anesthesia-recovery period may be an effective approach to manage adverse effects on brain development. This article is part of the special issue on 'Stress, Addiction and Plasticity'.
资助项目	National Natural Science Foundation of China[81971022] ; National Natural Science Foundation of China[31571040] ; Program of Shanghai Academic Research Leader[19XD1423300] ; Shanghai Municipal Commission of Education-Gaofeng Clinical Medicine[20191835]
WOS关键词	AWAKE-REGIONAL ANESTHESIA ; LONG-TERM POTENTIATION ; SILENT SYNAPSES ; GENERAL-ANESTHESIA ; INFANCY GAS ; SEVOFLURANE ; EXPRESSION ; PLASTICITY ; PERIOD ; MULTICENTER
WOS研究方向	Neurosciences & Neurology ; Pharmacology & Pharmacy
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000593895300007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296209]
专题	中国科学院上海药物研究所
通讯作者	Zhang, Xiaoyun; Zhou, Zikai
作者单位	1.Southeast Univ, Inst Life Sci, Key Lab Dev Genes & Human Dis, Minist Educ, Nanjing, Peoples R China 2.Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Shanghai Key Lab Psychot Disorders, Sch Med, Shanghai, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 4.Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Xiaoyun,Kong, Yue,He, Guiqin,et al. Neonatal exposure to ketamine disrupts developmental synapse unsilencing and predisposes adult mice for stressor-evoked anxiety[J]. NEUROPHARMACOLOGY,2020,180:12.
APA	Zhang, Xiaoyun,Kong, Yue,He, Guiqin,&Zhou, Zikai.(2020).Neonatal exposure to ketamine disrupts developmental synapse unsilencing and predisposes adult mice for stressor-evoked anxiety.NEUROPHARMACOLOGY,180,12.
MLA	Zhang, Xiaoyun,et al."Neonatal exposure to ketamine disrupts developmental synapse unsilencing and predisposes adult mice for stressor-evoked anxiety".NEUROPHARMACOLOGY 180(2020):12.