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活性调节细胞骨架相关蛋白(Arc)在 5-羟色胺转运体敲除大鼠中的表达改变和调节。

Altered expression and modulation of activity-regulated cytoskeletal associated protein (Arc) in serotonin transporter knockout rats.

机构信息

Center of Neuropharmacology, Department of Pharmacological Sciences, Universita' di Milano, Via Balzaretti 9, 20133 Milan, Italy.

出版信息

Eur Neuropsychopharmacol. 2009 Dec;19(12):898-904. doi: 10.1016/j.euroneuro.2009.06.008. Epub 2009 Jul 3.

Abstract

A gene variant in the human serotonin transporter (SERT) can increase the vulnerability to mood disorders. SERT knockout animals show similarities to the human condition and represent an important tool to investigate the mechanisms underlying the pathologic condition in humans. Along this line of thinking, we used SERT KO rats (SERT(+/-) and SERT(-/-)) to investigate abnormalities in the expression and function of the activity-regulated gene Arc (Activity-regulated cytoskeletal associated protein) and the early inducible gene Zif-268, (zinc finger binding protein clone 268), which are important players in neuronal plasticity. We found lower basal Arc mRNA levels in hippocampus and prefrontal cortex of mutant rats in comparison with wild-type animals. Moreover SERT mutant rats show altered stress responsiveness. Indeed an acute swim stress significantly up-regulated the levels of Arc mRNA in hippocampus and prefrontal cortex, as well as of Zif-268 in frontal cortex, only in SERT(+/-) and SERT(-/-) rats. These alterations may be associated to behavioral traits linked to SERT and may contribute to the neuroplastic and morphological changes observed in depression.

摘要

人类血清素转运蛋白(SERT)中的基因变异可增加患情绪障碍的易感性。SERT 敲除动物表现出与人类相似的特征,是研究人类病理状态下机制的重要工具。基于这种思路,我们使用 SERT KO 大鼠(SERT(+/-)和 SERT(-/-))来研究活性调节基因 Arc(活性调节细胞骨架相关蛋白)和早期诱导基因 Zif-268(锌指结合蛋白克隆 268)的表达和功能异常,这两个基因在神经元可塑性中起着重要作用。与野生型动物相比,我们发现突变型大鼠海马体和前额叶皮质中的基础 Arc mRNA 水平较低。此外,SERT 突变型大鼠表现出应激反应改变。事实上,急性游泳应激仅在 SERT(+/-)和 SERT(-/-)大鼠中显著上调了海马体和前额叶皮质中的 Arc mRNA 水平,以及额皮质中的 Zif-268 水平。这些变化可能与 SERT 相关的行为特征有关,并可能导致抑郁中观察到的神经可塑性和形态变化。

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