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血清和糖皮质激素诱导激酶3基因敲除小鼠的运动能力降低

Reduced locomotion in the serum and glucocorticoid inducible kinase 3 knock out mouse.

作者信息

Lang Undine E, Wolfer David P, Grahammer Florian, Strutz-Seebohm Nathalie, Seebohm Guiscard, Lipp Hans-Peter, McCormick James A, Hellweg Rainer, Dawson Kevin, Wang Jian, Pearce David, Lang Florian

机构信息

Department of Physiology I, Gmelinstr. 5, 72076 Tuebingen, Germany.

出版信息

Behav Brain Res. 2006 Feb 15;167(1):75-86. doi: 10.1016/j.bbr.2005.08.017. Epub 2005 Oct 24.

Abstract

The serum and glucocorticoid inducible kinase isoform SGK3 is expressed in the brain including hippocampal neurons. It is activated by phosphoinositide-3 (PI3) kinase and thus a putative target of neurotrophic factors. In vitro experiments pointed to the ability of SGK3 to regulate several transporters and ion channels including the AMPA receptor GluR1. In order to explore the in vivo functional significance of SGK3 in the regulation of spatial learning and exploratory behavior, we assessed the performance of SGK3 knockout mice (SGK3-/-) and their wild type littermates (SGK3+/+) in a place navigation task in the water-maze, radial maze in a battery of forced and free exploration tests, acoustic startle and a test for motoric coordination. According to water-maze and radial maze testing reference and working memory was intact in SGK3-/- mice. However, detailed analysis of swimming patterns of SGK3-/- mice in the water-maze revealed a deficit in precision and goal-directed navigation in space. SGK3-/- mice showed reduced exploratory activity, which was observed in several environments and increased centre field avoidance in the open-field. SGK3-/- mice further showed reduced darting behavior on open surfaces, indicating that the knock out may modify basic patterns of locomotion. In conclusion, lack of SGK3 leads to subtle behavioral defects which may result from deranged neuronal regulation of transporters and ion channels.

摘要

血清和糖皮质激素诱导激酶同工型SGK3在包括海马神经元在内的大脑中表达。它由磷酸肌醇-3(PI3)激酶激活,因此是神经营养因子的一个假定靶点。体外实验表明,SGK3具有调节多种转运体和离子通道的能力,包括AMPA受体GluR1。为了探究SGK3在调节空间学习和探索行为中的体内功能意义,我们评估了SGK3基因敲除小鼠(SGK3-/-)及其野生型同窝小鼠(SGK3+/+)在水迷宫中的位置导航任务、一系列强制和自由探索测试中的放射状迷宫、听觉惊吓以及运动协调性测试中的表现。根据水迷宫和放射状迷宫测试,SGK3-/-小鼠的参考记忆和工作记忆完好无损。然而,对SGK3-/-小鼠在水迷宫中的游泳模式进行详细分析后发现,它们在空间中的精确性和目标导向导航存在缺陷。SGK3-/-小鼠的探索活动减少,这在几种环境中都有观察到,并且在旷场实验中增加了对中央区域的回避。SGK3-/-小鼠在开放表面上的窜动行为也进一步减少,这表明基因敲除可能改变了基本的运动模式。总之,缺乏SGK3会导致细微的行为缺陷,这可能是由于转运体和离子通道的神经元调节紊乱所致。

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