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甘丙肽受体 2 过表达小鼠表现出抗抑郁样表型:可能涉及下托。

Galanin receptor 2 overexpressing mice display an antidepressive-like phenotype: possible involvement of the subiculum.

机构信息

Department of Neuroscience, Karolinska Institutet, Retzius Väg 8, S-17177 Stockholm, Sweden.

出版信息

Neuroscience. 2011 Sep 8;190:270-88. doi: 10.1016/j.neuroscience.2011.05.015. Epub 2011 Jun 13.

Abstract

The behavioral phenotype of a transgenic mouse overexpressing a galanin receptor 2 (GalR2)-enhanced, green fluorescent protein (EGFP)-construct under the platelet-derived growth factor-B promoter, and of controls, was assessed in various behavioral tests, such as the Porsolt forced swim test, as well as the open field, elevated plus maze and passive avoidance tests. In addition, the distribution of GalR2-EGFP expressing cell bodies and processes was studied in the brain of these mice using histochemical methods. Three age groups of the transgenic mice demonstrated decreased levels of immobility in the forced swim test, indicative of antidepressive-like behavior and/or increased stress resistance. Anxiety-like behaviors, measured in two different tests, did not differ between the GalR2-overexpressing and the wild-type mice, nor did motor activity levels, emotional learning or memory behaviors. High levels of GalR2 mRNA and protein expression were observed in the presubiculum, subiculum, cingulate cortex, retrosplenial granular and agranular cortices, subregions of prefrontal cortex, and the olfactory bulb, regions which are directly or indirectly implicated in depression-like behavior. These results may contribute to the understanding of the pathophysiology of major depressive disorder and the role of GalR2 in the regulation of mood, and suggest a potential therapeutic effect by targeting the GalR2 for treatment of depressive disorders.

摘要

过表达血小板衍生生长因子-B 启动子驱动的甘丙肽受体 2(GalR2)增强型绿色荧光蛋白(EGFP)构建体的转基因小鼠的行为表型,以及对照品的行为表型,在各种行为测试中进行了评估,例如强迫游泳试验,以及开阔场、高架十字迷宫和被动回避试验。此外,使用组织化学方法研究了这些小鼠大脑中 GalR2-EGFP 表达细胞体和突起的分布。三个年龄组的转基因小鼠在强迫游泳试验中表现出较低的不动水平,表明具有抗抑郁样行为和/或增加的应激抵抗。在两种不同的测试中,GalR2 过表达和野生型小鼠之间的焦虑样行为没有差异,运动活动水平、情绪学习或记忆行为也没有差异。在旁小叶、下托、扣带回皮质、后扣带回颗粒和无颗粒皮质、前额叶皮质的亚区以及嗅球中观察到 GalR2 mRNA 和蛋白表达水平升高,这些区域直接或间接参与抑郁样行为。这些结果可能有助于理解重性抑郁障碍的病理生理学以及 GalR2 在调节情绪中的作用,并提示通过针对 GalR2 治疗抑郁障碍具有潜在的治疗效果。

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