Repeated Nitrous Oxide Exposure Exerts Antidepressant-Like Effects Through Neuronal Nitric Oxide Synthase Activation in the Medial Prefrontal Cortex

doi:10.3389/fpsyt.2020.00837

	Repeated Nitrous Oxide Exposure Exerts Antidepressant-Like Effects Through Neuronal Nitric Oxide Synthase Activation in the Medial Prefrontal Cortex
	Liu, Wei 1; Li, Qian 1; Ye, Binglu 1; Cao, Hang 1; Shen, Fuyi 1; Xu, Zhendong 1; Du, Weijia 1; Guo, Fei 2; Liu, Jinqi 3; Li, Tianyu 2
刊名	FRONTIERS IN PSYCHIATRY
	2020-09-03
卷号	11 页码:11
关键词	nitrous oxide (N2O) depression mPFC burst firing neuronal nitric oxide synthase (nNOS) BDNF
ISSN号	1664-0640
DOI	10.3389/fpsyt.2020.00837
通讯作者	Zhang, Bing(bingozzz@126.com) ; Liu, Zhiqiang(drliuzhiqiang@163.com)
英文摘要	Clinical studies have demonstrated that exposure to the inhalational general anesthetic nitrous oxide (N2O) produces antidepressant effects in depressed patients. However, the mechanisms underlying the antidepressant effects of N2O remain largely unknown. Neuronal nitric oxide synthase (nNOS)-mediated nitric oxide (NO) synthesis is essential for brain function and underlies the molecular mechanisms of many neuromodulators. We hypothesized that activation of the nNOS/NO pathway in the medial prefrontal cortex (mPFC) might mediate the antidepressant effects of N2O. In this study, we revealed that repeated N2O exposure produced antidepressant-like responses in mice. Our mechanistic exploration showed that repeated N2O exposure increased burst firing activity and that the expression levels of BDNF with nNOS activation were dependent in the mPFC. In particular, the antidepressant-like effects of N2O were also antagonized by local nNOS inhibition in the mPFC. In summary, our results indicated that N2O exposure enhances BDNF expression levels and burst firing rates in an nNOS activation dependent manner, which might underlie the pharmacological mechanism of the antidepressant-like effects of N2O exposure. The present study appears to provide further mechanistic evidence supporting the antidepressant effects of N2O.
资助项目	National Natural Science Foundation[81771188] ; National Natural Science Foundation[31671049] ; National Natural Science Foundation[81971418] ; National Natural Science Foundation[81901376] ; Science and Technology Commission of Shanghai Municipality[14411966700] ; Science and Technology Commission of Shanghai Municipality[16411967400] ; China Postdoctoral Science Foundation[2017M621535] ; Ministry of Science and Technology[2013CB91060101] ; Shanghai Municipal Commission of Health and Family Planning[201740072] ; Fundamental Research Funds for the Central Universities[22120180534] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040302] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA120402140]
WOS关键词	NEUROTROPHIC FACTOR ; DEPRESSION ; KETAMINE ; DISORDERS ; HYPOTHALAMUS ; DYSFUNCTION ; INHIBITOR ; NUCLEUS
WOS研究方向	Psychiatry
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000572524600001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/291200]
专题	中国科学院上海药物研究所
通讯作者	Zhang, Bing; Liu, Zhiqiang
作者单位	1.Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Med, Dept Anesthesiol, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai, Peoples R China 3.MacDuffie Sch, Granby, MA USA 4.Tongji Univ, Shanghai Matern & Infant Hosp 1, Clin & Translat Res Ctr, Sch Med, Shanghai, Peoples R China 5.Tongji Univ, Sch Med, Anesthesia & Brain Funct Res Inst, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Liu, Wei,Li, Qian,Ye, Binglu,et al. Repeated Nitrous Oxide Exposure Exerts Antidepressant-Like Effects Through Neuronal Nitric Oxide Synthase Activation in the Medial Prefrontal Cortex[J]. FRONTIERS IN PSYCHIATRY,2020,11:11.
APA	Liu, Wei.,Li, Qian.,Ye, Binglu.,Cao, Hang.,Shen, Fuyi.,...&Liu, Zhiqiang.(2020).Repeated Nitrous Oxide Exposure Exerts Antidepressant-Like Effects Through Neuronal Nitric Oxide Synthase Activation in the Medial Prefrontal Cortex.FRONTIERS IN PSYCHIATRY,11,11.
MLA	Liu, Wei,et al."Repeated Nitrous Oxide Exposure Exerts Antidepressant-Like Effects Through Neuronal Nitric Oxide Synthase Activation in the Medial Prefrontal Cortex".FRONTIERS IN PSYCHIATRY 11(2020):11.