A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior

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	A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior
	Qi, Xiaoli; Lin, Wenjuan; Wang, Donglin; Pan, Yuqin; Wang, Weiwen; Sun, Meng; W. J. Lin
摘要	Our recent research demonstrates that the extracellular signal-regulated kinase (ERK) signal pathway is impaired in depressed animals, and such disruption is effectively reversed following antidepressant treatment. These results indicate that the ERK pathway may participate in the molecular mechanism of depression. To provide direct evidence for the potential role of the ERK pathway in depression, the present study using a sub-chronic regimen of ERK inhibition investigated the disparate role for the ERK cascade in two specific brain areas, the dorsal hippocampus (dHP) and the medial prefrontal cortex (mPFC). in the pathophysiology of depressive-like behavior. Rats were bilaterally implanted with cannulas in the dHP or mPFC and were microinjected with U0126, a specific inhibitor of ERK upstream activator, or vehicle for 7 consecutive days. The behavioral effects of the ERK pathway inhibition were examined in the open field, elevated plus maze, and saccharin preference test. The results showed that the inhibition of the ERK pathway in dHP resulted in anhedonia and anxiety-like behavior, and the ERK pathway inhibition in the mPFC induced anhedonia and locomotor impairment in rats. The phosphorylation of the cyclic AMP-responsive-element-binding protein (CREB) was decreased following the ERK pathway inhibition either in dHP or mPFC. These findings demonstrate that the ERK pathway in either the dHP or mPFC participates in the pathophysiology of the depressive-like behavior, and may have pivotal role in human depression.; Our recent research demonstrates that the extracellular signal-regulated kinase (ERK) signal pathway is impaired in depressed animals, and such disruption is effectively reversed following antidepressant treatment. These results indicate that the ERK pathway may participate in the molecular mechanism of depression. To provide direct evidence for the potential role of the ERK pathway in depression, the present study using a sub-chronic regimen of ERK inhibition investigated the disparate role for the ERK cascade in two specific brain areas, the dorsal hippocampus (dHP) and the medial prefrontal cortex (mPFC). in the pathophysiology of depressive-like behavior. Rats were bilaterally implanted with cannulas in the dHP or mPFC and were microinjected with U0126, a specific inhibitor of ERK upstream activator, or vehicle for 7 consecutive days. The behavioral effects of the ERK pathway inhibition were examined in the open field, elevated plus maze, and saccharin preference test. The results showed that the inhibition of the ERK pathway in dHP resulted in anhedonia and anxiety-like behavior, and the ERK pathway inhibition in the mPFC induced anhedonia and locomotor impairment in rats. The phosphorylation of the cyclic AMP-responsive-element-binding protein (CREB) was decreased following the ERK pathway inhibition either in dHP or mPFC. These findings demonstrate that the ERK pathway in either the dHP or mPFC participates in the pathophysiology of the depressive-like behavior, and may have pivotal role in human depression. (C) 2008 Elsevier B.V. All rights reserved.
关键词	ERK CREB Hippocampus Prefrontal cortex U0126 Depression
学科领域	生理心理学/生物心理学
	2009-05-16
语种	英语
发表期刊	BEHAVIOURAL BRAIN RESEARCH
ISSN	0166-4328
卷号	199 期号:2 页码:203-209
期刊论文类型	Article
收录类别	SCI
WOS记录号	WOS:000264953700005
引用统计	被引频次：66[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.psych.ac.cn/handle/311026/5143
专题	中国科学院心理研究所回溯数据库(1956-2010)
通讯作者	W. J. Lin
作者单位	Chinese Acad Sci, Key Lab Mental Hlth, Inst Psychol, Beijing 100101, Peoples R China
第一作者单位	中国科学院心理健康重点实验室
推荐引用方式 GB/T 7714	Qi, Xiaoli,Lin, Wenjuan,Wang, Donglin,et al. A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior[J]. BEHAVIOURAL BRAIN RESEARCH,2009,199(2):203-209.
APA	Qi, Xiaoli.,Lin, Wenjuan.,Wang, Donglin.,Pan, Yuqin.,Wang, Weiwen.,...&W. J. Lin.(2009).A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior.BEHAVIOURAL BRAIN RESEARCH,199(2),203-209.
MLA	Qi, Xiaoli,et al."A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior".BEHAVIOURAL BRAIN RESEARCH 199.2(2009):203-209.

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