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

Karen Kumakura, Hiroshi Nomura, Takeshi Toyoda, Koichi Hashikawa, Takuya Noguchi, Kohsuke Takeda, Hidenori Ichijo, Makoto Tsunoda, Takashi Funatsu, Daigo Ikegami, Minoru Narita, Tsutomu Suzuki, Norio Matsuki

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)313-320
Number of pages8
JournalNeuroscience Research
Volume66
Issue number3
DOIs
Publication statusPublished - 2010 Mar 1
Externally publishedYes

Keywords

  • Behavior
  • Behavioral test battery
  • Learning
  • Locomotor activity
  • MAPK
  • Motor coordination
  • Object recognition memory
  • Rotarod

ASJC Scopus subject areas

  • Neuroscience(all)

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