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Increased Cdk5/p35 activity in the dentate gyrus mediates depressive-like behaviour in rats
Zhu, Wei-Li; Shi, Hai-Shui; Wang, Shen-Jun; Xu, Chun-Mei; Jiang, Wen-Gao; Wang, Xi; Wu, Ping; Li, Qian-Qian; Ding, Zeng-Bo; Lu, Lin
关键词Butyrolactone Cdk5 chronic mild stress depression p35
刊名INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
2012-07-01
DOI10.1017/S1461145711000915
15期:6页:795-809
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Clinical Neurology ; Neurosciences ; Pharmacology & Pharmacy ; Psychiatry
资助者National Natural Science Foundation of China ; National Basic Research Program of China ; National Natural Science Foundation of China ; National Basic Research Program of China
研究领域[WOS]Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
关键词[WOS]CYCLIN-DEPENDENT KINASE-5 ; UNPREDICTABLE MILD STRESS ; AMYOTROPHIC-LATERAL-SCLEROSIS ; SIGNALING PATHWAY ; HIPPOCAMPAL NEUROGENESIS ; NEUROFIBRILLARY TANGLES ; NEUROTROPHIC FACTORS ; BUTYROLACTONE-I ; MOOD DISORDERS ; ANTIDEPRESSANT
英文摘要

Depression is one of the most pervasive and debilitating psychiatric diseases, and the molecular mechanisms underlying the pathophysiology of depression have not been elucidated. Cyclin-dependent kinase 5 (Cdk5) has been implicated in synaptic plasticity underlying learning, memory, and neuropsychiatric disorders. However, whether Cdk5 participates in the development of depressive diseases has not been examined. Using the chronic mild stress (CMS) procedure, we examined the effects of Cdk5/p35 activity in the hippocampus on depressive-like behaviour in rats. We found that CMS increased Cdk5 activity in the hippocampus, accompanied by translocation of neuronal-specific activator p35 from the cytosol to the membrane in the dentate gyrus (DG) subregion. Inhibition of Cdk5 in DG but not in the cornu ammonis 1 (CA1) or CA3 hippocampal subregions inhibited the development of depressive-like symptoms. Overexpression of p35 in DG blocked the antidepressant-like effect of venlafaxine in the CMS model. Moreover, the antidepressants venlafaxine and mirtazapine, but not the antipsychotic aripiprazole, reduced Cdk5 activity through the redistribution of p35 from the membrane to the cytosol in DG. Our results showed that the development of depressive-like behaviour is associated with increased Cdk5 activity in the hippocampus and that the Cdk5/p35 complex plays a key role in the regulation of depressive-like behaviour and antidepressant actions.

语种英语
所属项目编号30800362 ; 2007CB512302
资助者National Natural Science Foundation of China ; National Basic Research Program of China ; National Natural Science Foundation of China ; National Basic Research Program of China
WOS记录号WOS:000306035600007
引用统计
被引频次:26[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61482
专题中国药物依赖性研究所
作者单位Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Zhu, Wei-Li,Shi, Hai-Shui,Wang, Shen-Jun,et al. Increased Cdk5/p35 activity in the dentate gyrus mediates depressive-like behaviour in rats[J]. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY,2012,15(6):795-809.
APA Zhu, Wei-Li.,Shi, Hai-Shui.,Wang, Shen-Jun.,Xu, Chun-Mei.,Jiang, Wen-Gao.,...&Lu, Lin.(2012).Increased Cdk5/p35 activity in the dentate gyrus mediates depressive-like behaviour in rats.INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY,15(6),795-809.
MLA Zhu, Wei-Li,et al."Increased Cdk5/p35 activity in the dentate gyrus mediates depressive-like behaviour in rats".INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY 15.6(2012):795-809.
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