title: Circadian Gene Circuitry Predicts Hyperactive Behavior in a Mood Disorder Mouse Model.
abstract: Bipolar disorder, also known as manic-depressive illness, causes swings in mood and activity levels at irregular intervals. Such changes are difficult to predict, and their molecular basis remains unknown. Here, we use infradian (longer than a day) cyclic activity levels in αCaMKII (Camk2a) mutant mice as a proxy for such mood-associated changes. We report that gene-expression patterns in the hippocampal dentate gyrus could retrospectively predict whether the mice were in a state of high or low locomotor activity (LA). Expression of a subset of circadian genes, as well as levels of cAMP and pCREB, possible upstream regulators of circadian genes, were correlated with LA states, suggesting that the intrinsic molecular circuitry changes concomitant with infradian oscillatory LA. Taken together, these findings shed light onto the molecular basis of how irregular biological rhythms and behavior are controlled by the brain.
authors.affiliation: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Hagihara
authors.affiliation: ATR Computational Neuroscience Laboratories, Soraku-gun, Kyoto 619-0288, Japan.
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Horikawa
authors.affiliation: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Hironori K
authors.initials: HK
authors.lastname: Nakamura
authors.affiliation: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Juzoh
authors.initials: J
authors.lastname: Umemori
authors.affiliation: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Shoji
authors.affiliation: ATR Computational Neuroscience Laboratories, Soraku-gun, Kyoto 619-0288, Japan; Graduate School of Informatics, Kyoto University, Kyoto, Kyoto 606-8501, Japan.
authors.forename: Yukiyasu
authors.initials: Y
authors.lastname: Kamitani
authors.affiliation: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan; Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan. Electronic address: miyakawa@fujita-hu.ac.jp.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
mesh_terms: D000818:Animals; D001007:Anxiety; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics*; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology; D003863:Depression; D004195:Disease Models, Animal; D006579:Heterozygote; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008124:Locomotion / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D019964:Mood Disorders / Q000378:metabolism / Q000473:pathology*; D059467:Transcriptome
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C490430:Hivep2 protein, mouse; D000242:Cyclic AMP; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2