title: Hyperactivity in novel environment with increased dopamine and impaired novelty preference in apoptosis signal-regulating kinase 1 (ASK1)-deficient mice.
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.
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Karen
authors.initials: K
authors.lastname: Kumakura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nomura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Toyoda
authors.forename: Koichi
authors.initials: K
authors.lastname: Hashikawa
authors.forename: Takuya
authors.initials: T
authors.lastname: Noguchi
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Takeda
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ichijo
authors.forename: Makoto
authors.initials: M
authors.lastname: Tsunoda
authors.forename: Takashi
authors.initials: T
authors.lastname: Funatsu
authors.forename: Daigo
authors.initials: D
authors.lastname: Ikegami
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Norio
authors.initials: N
authors.lastname: Matsuki
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004777:Environment; D005106:Exploratory Behavior / Q000502:physiology*; D005239:Fear / Q000502:physiology; D006948:Hyperkinesis / Q000378:metabolism*; D048848:MAP Kinase Kinase Kinase 5 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009483:Neuropsychological Tests; D013997:Time Factors
chemical_list: D015102:3,4-Dihydroxyphenylacetic Acid; D048848:MAP Kinase Kinase Kinase 5; C482859:Map3k5 protein, mouse; D004298:Dopamine