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Hippocampal CA3 calcineurin activity participates in depressive-like behavior in rats
Zhu, Wei-Li1; Shi, Hai-Shui1,2; Wang, Shen-Jun1; Wu, Ping1; Ding, Zeng-Bo1; Lu, Lin1
关键词calcineurin chronic mild stress cyclosporine-A depression hippocampus mGluR2 3
刊名JOURNAL OF NEUROCHEMISTRY
2011-06-01
DOI10.1111/j.1471-4159.2011.07285.x
117期:6页:1075-1086
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Neurosciences
研究领域[WOS]Biochemistry & Molecular Biology ; Neurosciences & Neurology
关键词[WOS]GLUTAMATE-RECEPTOR ANTAGONIST ; UNPREDICTABLE MILD STRESS ; EXCITATORY AMINO-ACIDS ; ANIMAL-MODELS ; PYRAMIDAL NEURONS ; ANTIDEPRESSANT TREATMENT ; PSYCHIATRIC-DISORDERS ; PROTEIN PHOSPHATASE ; MAJOR DEPRESSION ; AGONIST LY354740
英文摘要

P>Calcineurin is a serine/threonine protein phosphatase that regulates neurotransmission, neuronal structure and plasticity, and neuronal excitability in mood disorders, including depression. Increasing evidence has suggested that calcineurin is involved in the regulation of depressive-like behavior. However, little is known about the neurobiological mechanisms that underlie the mood-regulating effects of calcineurin. We investigated the potential mechanism by which calcineurin mediates the development of depressive-like behavior and the involvement of calcineurin in the action of antidepressant medication in the chronic mild stress (CMS) model. The results showed that rats exposed to CMS had decreased calcineurin activity, measured by increased phospho-synapsin I S62/67 (pSynapsin) and decreased calcineurin-A alpha levels, specifically in the CA3 but not CA1 or dentate gyrus (DG) subfields of the hippocampus. Calcineurin inhibition in the CA3 but not DG by microinfusion of cyclosporine-A (2 mu g) induced depressive-like behavior in normal rats and exacerbated depressive-like performance in CMS-treated rats. Additionally, calcineurin inhibition in the CA3 but not DG reversed the antidepressant-like activity of venlafaxine. Calcineurin inhibition in the CA3 also reduced metabotropic glutamate 2/3 receptor (mGluR2/3) expression levels. mGluR2/3 activation by its agonist LY354740 (100 ng) in the CA3 reversed the depressive-like behavior induced by cyclosporine-A administration. Finally, chronic venlafaxine (40 mg/kg) treatment increased calcineurin activity, reflected by decreased pSynapsin and increased calcineurin-A alpha protein levels in the CA3 but not CA1 or DG. These findings indicate that CA3 calcineurin signaling probably mediated through mGluR2/3 participates in the development of depression and the behavioral responses to antidepressant treatment.

语种英语
WOS记录号WOS:000291223800014
项目编号30800362 ; 2007CB512302
资助机构National Natural Science Foundation of China ; National Basic Research Program of China
引用统计
被引频次:20[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/400002259/58458
专题北京大学医学部管理机构_医学部
中国药物依赖性研究所
作者单位1.Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
2.Hebei Med Univ, Basic Med Coll, Dept Biochem & Mol Biol, Shijiazhuang, Peoples R China
推荐引用方式
GB/T 7714
Zhu, Wei-Li,Shi, Hai-Shui,Wang, Shen-Jun,et al. Hippocampal CA3 calcineurin activity participates in depressive-like behavior in rats[J]. JOURNAL OF NEUROCHEMISTRY,2011,117(6):1075-1086.
APA Zhu, Wei-Li,Shi, Hai-Shui,Wang, Shen-Jun,Wu, Ping,Ding, Zeng-Bo,&Lu, Lin.(2011).Hippocampal CA3 calcineurin activity participates in depressive-like behavior in rats.JOURNAL OF NEUROCHEMISTRY,117(6),1075-1086.
MLA Zhu, Wei-Li,et al."Hippocampal CA3 calcineurin activity participates in depressive-like behavior in rats".JOURNAL OF NEUROCHEMISTRY 117.6(2011):1075-1086.
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