Document Detail


Hyperactivity in novel environment with increased dopamine and impaired novelty preference in apoptosis signal-regulating kinase 1 (ASK1)-deficient mice.
MedLine Citation:
PMID:  20006657     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
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Publication Detail:
Type:  Journal Article     Date:  2009-12-16
Journal Detail:
Title:  Neuroscience research     Volume:  66     ISSN:  1872-8111     ISO Abbreviation:  Neurosci. Res.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-17     Completed Date:  2010-06-07     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  8500749     Medline TA:  Neurosci Res     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  313-20     Citation Subset:  IM    
Affiliation:
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
3,4-Dihydroxyphenylacetic Acid / metabolism*
Animals
Brain / metabolism*
Dopamine / metabolism*
Environment
Exploratory Behavior / physiology*
Fear / physiology
Hyperkinesis / metabolism*
MAP Kinase Kinase Kinase 5 / deficiency,  genetics,  metabolism*
Male
Memory / physiology
Memory Disorders / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Motor Activity / physiology
Neuropsychological Tests
Time Factors
Chemical
Reg. No./Substance:
102-32-9/3,4-Dihydroxyphenylacetic Acid; EC 2.7.11.25/MAP Kinase Kinase Kinase 5; EC 2.7.11.25/Map3k5 protein, mouse

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