title: Cryptochrome-dependent circadian periods in the arcuate nucleus.
abstract: The circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus is responsible for controlling behavioral activity rhythms, such as a free running rhythm in constant darkness. Rodents have several circadian oscillators in other brain regions including the arcuate nucleus (ARC). In specific conditions such as food anticipatory activity rhythms in the context of timed restricted feeding, an alternative circadian pace-making system has been assumed by means of circadian oscillators like the SCN. Despite extensive lesion studies, the anatomic locations of extra-SCN circadian pacemakers responsible for regulating behavioral rhythms have not been found. In the present study, we investigated circadian rhythms in the SCN and extra-SCN region of the arcuate nucleus (ARC) by analyzing PER2::LUCIFERASE expression in specific regions from wild-type C57BL/6, Cry1(-/-), and Cry2(-/-) mice. Compared to wild-type animals, we observed period shortening in both the SCN and ARC of Cry1(-/-) mice and period lengthening in Cry2(-/-) mice. Interestingly, the periods in the ARC of both genotypes were identical to those in the SCN. Moreover, the amplitudes of PER2::LUC rhythms in the ARC of all animals were decreased compared to those in the SCN. These data suggest that the ARC is a candidate circadian pacemaker outside the SCN.
authors.affiliation: Laboratory of Oral Chronobiology, Graduate School of Dentistry, Osaka University, Suita, Osaka 565-0871, Japan; Department of Oral-Facial Disorders, Graduate School of Dentistry, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Uchida
authors.affiliation: Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki, Kanagawa 214-8571, Japan; Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Tokyo 164-8530, Japan.
authors.forename: Takahiro J
authors.initials: TJ
authors.lastname: Nakamura
authors.affiliation: Laboratory of Oral Chronobiology, Graduate School of Dentistry, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Nana N
authors.initials: NN
authors.lastname: Takasu
authors.affiliation: Department of Radiation Biology and Medical Genetics, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Todo
authors.affiliation: Department of Oral-Facial Disorders, Graduate School of Dentistry, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Laboratory of Oral Chronobiology, Graduate School of Dentistry, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address: wataru@dent.osaka-u.ac.jp.
authors.forename: Wataru
authors.initials: W
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000502:physiology*; D002940:Circadian Rhythm; D056931:Cryptochromes / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D056950:Period Circadian Proteins / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000502:physiology
chemical_list: C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; D056931:Cryptochromes; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins
keywords: Arcuate nucleus; Behavioral activity; Circadian rhythm; Clock genes; Suprachiasmatic nucleus