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, 66 (3), 313-20

Hyperactivity in Novel Environment With Increased Dopamine and Impaired Novelty Preference in Apoptosis Signal-Regulating Kinase 1 (ASK1)-deficient Mice

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Hyperactivity in Novel Environment With Increased Dopamine and Impaired Novelty Preference in Apoptosis Signal-Regulating Kinase 1 (ASK1)-deficient Mice

Karen Kumakura et al. Neurosci Res.

Abstract

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 ASK1 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 24h after training and superior performance on 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.

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