Hyperactivity in novel environment with increased dopamine and impaired novelty preference in apoptosis signal-regulating kinase 1 (ASK1)-deficient mice

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...

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Veröffentlicht in:Neuroscience research 2010-03, Vol.66 (3), p.313-320
Hauptverfasser: Kumakura, Karen, Nomura, Hiroshi, Toyoda, Takeshi, Hashikawa, Koichi, Noguchi, Takuya, Takeda, Kohsuke, Ichijo, Hidenori, Tsunoda, Makoto, Funatsu, Takashi, Ikegami, Daigo, Narita, Minoru, Suzuki, Tsutomu, Matsuki, Norio
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Sprache:eng
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Zusammenfassung: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 24 h 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.
ISSN:0168-0102
1872-8111
DOI:10.1016/j.neures.2009.12.003