Dear friends:

We are studying on mammalian circadian rhythms:

The center of the mammalian circadian clock lies in the suprachiasmatic nucleus (SCN). The environmental 24 h light : dark cycle entrains the circadian center. The circadian center supervises peripheral physiological events by resetting the peripheral oscillators. Therefore, not only the oscillating mechanism that resides in the SCN but also input and output systems of the SCN are objects of our research.

We are studying the underlying molecular mechanisms that maintain the mammalian circadian clock system. Recently we found that jet lag syndrome is associated with the dissociation of the circadian center (Nagano et al. 2003). We also revealed the molecular mechanism that makes the night of the circadian clock (Ueda et al. 2002).There are many unsolved problems in the field. I hope that many students will join our group and enjoy the scientific investigation and chronobiology.

Yasufumi Shigeyoshi M.D. Ph.D Professor, Department of Anatomy and Neurobiology Kinki University School of Medicine 377-2 Ohno-Higashi, Osakasayama City, Osaka 589-8511, Japan E-mail: shigey@med.kindai.ac.jp

The mechanism of jet lag

Schematic representation of the dissociation and slow resynchronization of endogenous oscillators within the rat SCN after an LD cycle shift.

A rapid shift of light: dark cycle dissociates the suprachiasmatic nucleus (SCN), the mammalian circadian center. Light-responsive clocks in the ventrolateral region of the SCN shifts rapidly while the light-unresponsive ones in the dorsomedial region shift very slowly. During the desynchrony, the locomotor activity of animals shows increased nighttime rest, showing the jet lag of animals. It takes 5 to 10 days for rats to obtain steady circadian rhythm of locomotor activity and resynchronization of the SCN. OC, Optic chiasm; III, the third ventricle.

Papers published recently are:

2011年

・Kitazawa M, Nagano KH, Shigeyoshi Y, Natsume T, Hashimoto S. Angiopoietin-Like 2, a Circadian Gene, Improves Type 2 Diabetes Through Potentiation of Insulin Sensitivity in Mice Adipocytes. Endocrinology 2011 May 17 (Epub ahead of print)

2010年

・Fuke S, Kubota M, Kasahara T, Shigeyoshi Y, Kato T. Regional variation in mitochondrial DNA copy number in mouse brain. Biochim Biophys Acta. 2010 Dec 7. 1807(3):270-4.

・Masumoto KH, Ukai-Tadenuma M, Kasukawa T, Nagano M, Uno KD, Tsujino K, Horikawa K, Shigeyoshi Y, Ueda HR. Acute Induction of Eya3 by Late-Night Light Stimulation Triggers TSHβ Expression in Photoperiodism. Curr Biol. 2010 Dec 1. 20(24):2199-2206

・Yagita K, Horie K, Koinuma S, Nakamura W, Yamanaka I, Urasaki A, Shigeyoshi Y, Kawakami K, Shimada S, Takeda J, Uchiyama Y. Development of the circadian oscillator during differentiation of mouse embryonic stem cells in vitro. proc Natl .Acad .Sci .U S A 2010 Feb 23 ;107(8):3846-51.

2009年

・Mamoru Nagano, Akihito Adachi, Koh-hei Masumoto, Elizabeth Meyer-Bernstein, and Yasufumi Shigeyoshi rPer1 and rPer2 induction during phases of the circadian cycle critical for light resetting of the circadian clock, Brain research, in press

・NItta Y, Shigeyoshi Y, Nakagata N, Kaneko T, Nitta K, Harada T, Ishizaki F, and Townsend J. Kinetics of blood glucose in mice carrying hemizygous Pax6. Exp. Anim. 2009 58(2);105-112

・Koinuma S, Yagita K, Fujioka A, Takashima N, Takumi T, Shigeyoshi Y. The resetting of the circadian rhythm by Prostaglandin J(2) is distinctly phase-dependent.FEBS Lett. 2009 583(2):413-8

2008

・Koinuma S, Yagita K, Fujioka A, Takashima N, Takumi T, Shigeyoshi Y. The resetting of the circadian rhythm by Prostaglandin J(2) is distinctly phase-dependent.FEBS Lett. 2009 583(2):413-8

・Hayasaka N*, Akashi M*, Yamazaki S, Node K. (*co-first authors)Mitogen-activated protein kinase is a functional component of theautonomous circadian system in the suprachiasmatic nucleus. J Neurosci. 2008 Apr 30;28(18):4619-23.

・Kumaki Y, Ukai-Tadenuma M, Uno KD, Nishio J, Masumoto KH, Nagano M, Komori T, Shigeyoshi Y, Hogenesch JB, Ueda HR. Analysis and synthesis of high-amplitude Cis-elements in the mammalian circadian clock.
Proc Natl Acad Sci U S A. 2008 105(39) 14946-51.

・Takahashi Y, Takahashi M, Carpino N, Jou ST, Chao JR, Tanaka S, Shigeyoshi Y, Parganas E, Ihle JN. Leukemia inhibitory factor regulates trophoblast giant cell differentiation via Janus kinase 1-signal transducer and activator of transcription 3-suppressor of cytokine signaling 3 pathway. Mol Endocrinol. 2008 22(7) 1673-81.

・Terazono H, Hamdan A, Matsunaga N, Hayasaka N, Kaji H, Egawa T, Makino K, Shigeyoshi Y, Koyanagi S, Ohdo S. Modulatory effects of 5-fluorouracil on the rhythmic expression of circadian clock genes: a possible mechanism of chemotherapy-induced circadian rhythm disturbances. Biochem Pharmacol. 2008 75(8) 1616-22

2007

・Fujinaga R, Yanai A, Nakatsuka H, Yoshida K, Takeshita Y, Uozumi K, Zhao C, Hirata K, Kokubu K, Nagano M, Shinoda K. Anti-human placental antigen complex X-P2 (hPAX-P2) anti-serum recognizes C-terminus of huntingtin-associated protein 1A common to 1B as a determinant marker for the stigmoid body. Histochem Cell Biol. 128(4):335-48,2007 .

・Ukai H, Kobayashi1 TJ, Nagano M, Masumoto K, Mitsugu S, Kondo T, Yagita K, Shigeyoshi Y and Ueda H R Melanopsin-dependent photo-perturbation reveals desynchronization underlying the singularity of mammalian circadian clocks. Nature Cell Biology 9, 1327-1334,2007

・Sujino M, Nagano M , Fujioka A , Shigeyoshi Y and Inouye ST Temporal profile of circadian clock gene expression in a transplanted suprachiasmatic nucleus and peripheral tissues. European Journal of neuroscience 26(10)2731-8, 2007

・Yamanaka I, Koinuma S, Shigeyoshi Y, Uchiyama Y, Yagita K. Presence of robust circadian clock oscillation under constitutive over-expression of mCry1 in rat-1 fibroblasts. FEBS Lett. 581(21):4098-102, 2007

・Kojima S, Matsumoto K, Hirose M, Shimada M, Nagano M, Shigeyoshi Y, Hoshino SI, Ui-Tei K, Saigo K, Green CB, Sakaki Y, Tei H. LA activates posttranscriptional expression of an essential mammalian clock protein, PERIOD1. Proc Natl Acad Sci U S A. 104:1859-1864 , 2007

2006

・Takashima N, Fujioka A, Hayasaka N, Matsuo A, Takasaki J & Shigeyoshi Y Gq/11-induced intracellular calcium mobilization mediates Per2 acute induction in Rat-1 fibroblasts Genes to Cells 11(9):1039-49 2006

・ Fujioka A, Takashima N and Shigeyoshi Y. Circadian rhythm generation in a glioma cell line. Biochem Biophys Res Commun. 346(1):169-174, 2006

・ Masumoto KH, Nagano M, Takashima N, Hayasaka N, Hiyama H, Matsumoto S, Inouye ST, and Shigeyoshi Y. Distinct localization of prokineticin 2 and prokineticin receptor 2 mRNAs in the rat suprachiasmatic nucleus. Eur J Neurosci. 23(11):2959-2970, 2006

・ Matsumoto S, Yamazaki C, Masumoto KH, Nagano M, Naito M, Soga T, Hiyama H, Matsumoto M, Takasaki J, Kamohara M, Matsuo A, Ishii H, Kobori M, Katoh M, Matsushime H, Furuichi K, and Shigeyoshi Y. Abnormal development of the olfactory bulb and reproductive system in mice  lacking prokineticin receptor PKR2. Proc Natl Acad Sci U S A. 103(11), 4140:4145, 2006 

2005

・ Ueda HR, Hayashi S, Chen W, Sano M, Machida M, Shigeyoshi Y, Iino M, Hashimoto S. System-level identification of transcriptional circuits underlying mammalian circadian clocks. Nat Genet. 2005 37(2):187-192. 2005

・Matsuo A, Matsumoto SI, Nagano M, Masumoto KH, Takasaki J, Matsumoto M, Kobori M, Katoh ハM, Shigeyoshi Y. Molecular cloning and characterization of a novel Gq-coupled orphan receptor GPRg1 exclusively expressed in the central nervous system. Biochem Biophys Res Commun. 27;331(1):363-369. 2005

・Ito H., Ito Hidefumi, Nagano M., Nakano S., Nakano S., Shigeyoshi Y., and Kusaka H. In situ Identification of Hepatitis C Virus RNA in muscle. Neurology 64(6): 1073-1075. 2005

・Hayasaka H, Simon K, Hershey ED, Masumoto KH, Parsons JT. FRNK, the autonomously expressed C-terminal region of focal adhesion kinase, is uniquely regulated in vascular smooth muscle: Analysis of expression in transgenic mice. J Cell Biochem. 2005 Aug 15;95(6):1248-63.

・Hayasaka N,Larue SI, Green CB. Genetic manipulation of circadian fhythms in Xenopus. Methods Enzymol. 393:205-19(2005)

2004

・Fujinaga R, Kawano J, Matsuzaki Y, Kamei K, Yanai A, Sheng Z, Tanaka M, Nakahama K, Nagano M, Shinoda K.?Neuroanatomical distribution of Huntingtin-associated protein 1-mRNA in the male mouse brain. J Comp Neurol. 2004 Oct 4;478(1):88-109.

Satoh, S., Matsumura, H., Fujioka, A., Nakajima, T., Kanbayashi, T., Nishino, S., Shigeyoshi, Y., Yoneda, H. FOS expression in orexin neurons following muscimol perfusion of preoptic area. Neuroreport,15, 1127-1131 (2004)

Iwasaki, T., Ken-ichi Nakahama, K., Mamoru Nagano M., Atsuko Fujioka A., Harumasa Ohyanagi, H., Yasufumi Shigeyoshi, Y. A partial hepatectomy results in altered expression of clock-related and cyclic glyceraldehyde 3--phosphate dehydrogenase (GAPDH) genes. Life Sciences, 74,3093-3102(2004)

2003

Kawamoto, K., Nagano, M., Kanda, F., Chihara, K., Shigeyoshi, Y., Okamura, H. Two types of VIP neuronal components in rat suprachiasmatic nucleus. J Neurosci. Res. 74, 852-857. (2003)

Nagano, M., Adachi, A., Nakahama, K., Nakamura, T., Tamada, M., Meyer-Bernstein, E., Sehgal, A, and Shigeyoshi, Y. An abrupt shift in the day:night cycle causes desynchrony in the mammalian circadian center. J. Neurosci. 23, 6141-6151 (2003)

Masumoto K.H., Fujioka A., Nakahama K., Inouye S.T., Shigeyoshi Y. Effect of phosphodiesterase type 4 on circadian clock gene Per1 transcription. Biochem Biophys Res Commun. 306, 781-785 (2003)

Satoh S, Nakahama K, Shigeyoshi Y., et al Inhibition of rostral basal forebrain neurons neurons promtes wakefulness and induces FOS in orexin neurons. Eur. J. Neurosci. 17(8):1635-45,2003

2002

Ueda HR, Chen W, Adachi A, Wakamatsu H, Hayashi S, Takasugi T, Nagano M, Nakahama K, Suzuki Y, Sugano S, Iino M, Shigeyoshi Y, Hashimoto S. A transcription factor response element for gene expression during circadian night. Nature. 418(6897): 534-9.2002

Nakahama K, Fujioka A, Nagano M, Satoh S, Furukawa K, Sasaki H, Shigeyoshi Y. A role of the C-terminus of aquaporin 4 in its membrane expression in cultured astrocytes. Genes Cells. 2002 7(7):731-41.

Shigeyoshi Y, Meyer-Bernstein E, Yagita K, Fu W, Chen Y, Takumi T, Schotland P,Sehgal A, Okamura H. Restoration of circadian behavioural rhythms in a period null Drosophila mutant (per01) by mammalian period homologues mPer1 and mPer2. Genes Cells 7(2):163-171,2002

Hayasaka N., LaRue SL, Green CB. In vivo disruption of Xenopus CLOCK in te retinal photoreceptor cells abolishes circadian melatonin rythmicity without affecting its production levels. J. Neurosci. 22(5):1600-7 ,2002

2001

Constitutive expression and delayed light response of casein kinase Iepsilon and Idelta mRNAs in the mouse suprachiasmatic nucleus.(Ishida, Y., Yagita, K., Fukuyama, T., Nishimura, M., Nagano, M., Shigeyoshi, Y., Yamaguchi, S., Komori, T., and Okamura, H. J. Neurosci. Res. 64, 612-616 ,2001)

Expression of the Per1 gene in the Hamster: Brain Atlas and Circadian Characteristics in the Suprachiasmatic Nucleus. Yamamoto, S., (Shigeyoshi, Y., Ishida, Y., Fukuyama, T., Yamaguchi, S., Yagita, K., Moriya, Y., Shibata, S., Yakashima, N., and Okamura, H J. Comp. Neurol. 430, 518-532 ,2001)

Different developmental profiles of the expression of preprosomatostatin and preprotachykinin-A mRNAs in rat SCN neurons. ( Nakamura, T., Shigeyoshi, Y., Maebayashi, Y., Yamaguchi, S., Yagita, K., and Okamura, Dev. Brain Research, 127, 81-86 ,2001)

Different Circadian Expression Profiles of Clock Genes in the Mouse Suprachiasmatic Nucleus(K. Taguchi, R. Okura, K. Yagita, Y. Ishida, H. Onishi, Y. Shigeyoshi, S. Yamaguchi,M. Nishimura, S Masubuchi,and H. Okamura、Biomedical Research 22 (3) 125-131, 2001)

1999

The relationship between ocular melatonin and dopamine rhythms in the pigeon: effects of melatonin inhibition on dopamine release. (Adachi A, Suzuki Y, Nogi T, Ebihara S. Brain Res., 815(2):435-440, 1999)

A putative transcription factor with seven zinc-finger motifs identified in the developing suprachiasmatic nucleus by the differential display-PCR method. (Maebayashi, Y., Shigeyoshi, Y., Takumi, T. and Okamura, H. J. Neurosci. 15: 10176-10183, 1999)

Per1 and Per2 gene expression in the rat suprachiasmatic nucleus: circadian profile and the compartment-specific response to light. (Yan, L., Takekida, S.,Shigeyoshi, Y., and Okamura, H. Neuroscience 94: 141-150 1999)

Localization of calbindin D 28k in MDBK cells. Fujioka, K.Nakahama, M.Nagano,H.Sasaki. Recent Development of Electron Microscopy 1998 119-122,1999)

Effect of TPA on aquaporin4 mRNA expression in cultured astrocytes. ( K.Nakahama, M.Nagano, A.Fujioka, K.Shinoda, H.Sasaki. GLIA 25 : 240-246,1999)

Region-dependent difference in the sleep-promoting potency of an adenosine A2A receptor agonist. (Satoh S., Matsumura H., Koike N., Tokunaga Y., Maeda T., Hayaishi O. Eur J Neurosci 1999 May;11(5):1587-97)

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