Hyperactivity in novel environment with increased dopamine and impaired novelty preference in apoptosis signal-regulating kinase 1 (ASK1)-deficient mice
Hyperactivity in novel environment with increased dopamine and impaired novelty preference in apoptosis signal-regulating kinase 1 (ASK1)-deficient mice
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DOI：
10.1016/j.neures.2009.12.003
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发表时间：
2010-03-01
影响因子：
2.9
通讯作者：
Matsuki, Norio
中科院分区：
文献类型：
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作者：
Kumakura, Karen;Nomura, Hiroshi;Matsuki, Norio
凋亡信号调节激酶1（apoptosis signal-regulating kinase 1，ASK 1）是丝裂原活化蛋白激酶（mitogen-activated protein kinase kinase kinase kinase kinase kinase）家族成员，通过JNK和p38 MAP激酶级联途径诱导多种细胞凋亡。除了凋亡信号外，最近的一些体外研究表明ASK 1可能在神经功能中发挥作用。然而，ASK 1的行为学意义尚不清楚。我们对ASK 1（-/-）小鼠进行了一系列行为测试，发现它们在旷场测试中表现出暂时的活动过度。在熟悉的领域中的活动是正常的，表明观察到的活动过度是新环境特有的。ASK 1（-/-）小鼠在训练后24 h也表现出新奇偏好的损害，并且在旋转棒测试中表现出上级表现。在ASK 1（-/-）小鼠中，脑组织中多巴胺和4-二羟基苯乙酸（DOPAC）的含量升高。(C)2009爱思唯尔爱尔兰有限公司和日本神经科学学会版权所有
Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein (MAP) kinase kinase kinase family member, which induces apoptosis in various cells through JNK and p38 MAP kinase cascades In addition to apoptosis signaling, a number of recent in vitro studies have suggested that ASK 1 may play roles in neural function However, the behavioral significance of ASK1 has remained unclear Here, we subjected ASK1 (-/-) mice to a battery of behavioral tests and found that they displayed temporary hyperactivity in an open-field test Activities in the familiar field were normal, indicating that the hyperactivity observed was specific to the novel environment. ASK1 (-/-) mice also exhibited impairment of novelty preference 24 h after training and superior performance oil the rotarod test Brain tissue contents of dopamine and 4-dihydroxyphenylacetic acid (DOPAC) were elevated in ASK1 (-/-) mice Our findings thus demonstrate novel behavioral functions of ASK1, including regulation of locomotor activity, novelty preference, and motor coordination with dopaminergic transmission. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society All rights reserved