Involvement of cyclin-dependent kinase-like 2 in cognitive function required for contextual and spatial learning in mice
Involvement of cyclin-dependent kinase-like 2 in cognitive function required for contextual and spatial learning in mice
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DOI：
10.3389/fnbeh.2010.00017
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发表时间：
2010-01-01
影响因子：
3
通讯作者：
Itohara, Shigeyoshi
中科院分区：
文献类型：
--
作者：
Gomi, Hiroshi;Sassa, Takayuki;Itohara, Shigeyoshi
细胞周期蛋白依赖性激酶样 2 (Cdkl2) 是一种与 cdc2 相关的丝氨酸/苏氨酸蛋白激酶，出生后在各个大脑区域表达，包括大脑皮层、内嗅皮层、海马、杏仁核和背侧丘脑。这些区域中极高的 Cdkl2 表达表明它在认知和情感中发挥作用。最近的遗传学研究表明，Cdk1 家族激酶的突变与人类的神经发育和神经精神疾病有关。为了阐明 Cdkl2 的生理作用，我们对缺乏 Cdkl2 的 Cdkl2(LacZ/LacZ) 小鼠进行了行为分析。 Cdkl2(LacZ/LacZ)小鼠在抑制性回避任务中电足电击后进入暗室的潜伏期减少，并且在暴露于温和的训练条件时减弱了背景恐惧反应。莫里斯水迷宫中的海马空间学习略有异常，小鼠表现出异常的游泳模式。双向回避任务中的厌恶反应略有增强，但不显着。另一方面，Cdkl2(LacZ/LacZ)小鼠没有表现出对厌恶刺激的敏感性改变，例如电击和热，或者在高架十字迷宫或旋转杆测试中的缺陷。这些发现表明Cdkl2参与认知功能，并为小鼠终末分化神经元中表达的Cdkl家族激酶的功能提供体内证据。
Cyclin-dependent kinase-like 2 (Cdkl2) is a cdc2-related serine/threonine protein kinase that is postnatally expressed in various brain regions, including the cerebral cortex, entorhinal cortex, hippocampus, amygdala, and dorsal thalamus. The extremely high Cdkl2 expression in these regions suggests that it has a role in cognition and emotion. Recent genetic studies indicate that mutations of Cdkl family kinases are associated with neurodevelopmental and neuropsychiatric disorders in humans. To elucidate the physiologic role of Cdkl2, we behaviorally analyzed Cdkl2(LacZ/LacZ) mice lacking Cdkl2. Cdkl2(LacZ/LacZ) mice had reduced latencies to enter the dark compartment after electric footshock in an inhibitory avoidance task and attenuated contextual fear responses when exposed to mild training conditions. Hippocampal spatial learning in the Morris water maze was slightly anomalous with mice exhibiting an abnormal swimming pattern. The aversive response in a two-way avoidance task was slightly, but not significantly, enhanced. On the other hand, Cdkl2(LacZ/LacZ) mice did not exhibit altered sensitivity to aversive stimuli, such as electric footshock and heat, or deficits in the elevated plus maze or rotating rod test. These findings suggest that Cdkl2 is involved in cognitive function and provide in vivo evidence for the function of Cdkl family kinases expressed in terminally differentiated neurons in mice.