GAL3 receptor KO mice exhibit an anxiety-like phenotype
GAL3 receptor KO mice exhibit an anxiety-like phenotype
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DOI：
10.1073/pnas.1318066111
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发表时间：
2014-05-13
影响因子：
11.1
通讯作者：
Kofler, Barbara
中科院分区：
文献类型：
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作者：
Brunner, Susanne M.;Farzi, Aitak;Kofler, Barbara
甘丙肽（galanin， GAL）广泛分布于中枢和周围神经系统。它是多种生理和病理过程的调节剂，通过三种G蛋白偶联受体（GAL（1-3）受体）介导其作用。由于GAL及其受体在啮齿动物的大脑边缘结构中高度表达，因此GAL可能是情绪和焦虑的调节剂。近年来，大量动物模型研究表明，GAL和GAL(1)和GAL(2)受体参与焦虑和抑郁相关行为。然而，迄今为止，很少有文献表明GAL(3)受体与行为功能有关。因此，我们研究了GAL(3)受体缺陷（GAL(3)-KO）小鼠的行为，以阐明GAL(3)受体是否参与介导GAL的行为相关作用。GAL(3)-KO小鼠系表现出正常的繁殖和身体发育。除了行为测试外，表型表征还包括血液学、氨基酸谱、代谢和sudomotor功能的分析。与WT幼崽相比，雄性GAL(3)-KO小鼠在高架迷宫、开阔场地和光/暗盒测试中表现出焦虑样表型，在社交互动测试中，它们对陌生小鼠的社会依恋程度低于WT动物。总之，我们的数据表明，GAL(3)受体参与了GAL介导的情绪、焦虑和行为的影响，使其成为情绪障碍替代治疗策略的可能靶点。
The neuropeptide galanin (GAL) is widely distributed in the central and peripheral nervous systems. It is a modulator of various physiological and pathological processes, and it mediates its effects via three G protein-coupled receptors (GAL(1-3) receptors). A role for GAL as a modulator of mood and anxiety was suggested, because GAL and its receptors are highly expressed in limbic brain structures of rodents. In recent years, numerous studies of animal models have suggested an involvement of GAL and GAL(1) and GAL(2) receptors in anxiety-and depression-related behavior. However, to date, there is sparse literature implicating GAL(3) receptors in behavioral functions. Therefore, we studied the behavior of GAL(3) receptor-deficient (GAL(3)-KO) mice to elucidate whether GAL(3) receptors are involved in mediating behavior-associated actions of GAL. The GAL(3)-KO mouse line exhibited normal breeding and physical development. In addition to behavioral tests, phenotypic characterization included analysis of hematology, amino acid profiles, metabolism, and sudomotor function. In contrast to WT littermates, male GAL(3)-KO mice exhibited an anxiety-like phenotype in the elevated plus maze, open field, and light/dark box tests, and they were less socially affiliated than WT animals to a stranger mouse in a social interaction test. In conclusion, our data suggest involvement of GAL(3) receptors in GAL-mediated effects on mood, anxiety, and behavior, making it a possible target for alternative treatment strategies for mood disorders.