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 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.
Kumakura
Karen
K
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Nomura
Hiroshi
H
Toyoda
Takeshi
T
Hashikawa
Koichi
K
Noguchi
Takuya
T
Takeda
Kohsuke
K
Ichijo
Hidenori
H
Tsunoda
Makoto
M
Funatsu
Takashi
T
Ikegami
Daigo
D
Narita
Minoru
M
Suzuki
Tsutomu
T
Matsuki
Norio
N
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
D015102:3,4-Dihydroxyphenylacetic Acid; D048848:MAP Kinase Kinase Kinase 5; C482859:Map3k5 protein, mouse; D004298:Dopamine