Grant-in-Aid for Scientific Research (S)
|Allocation Type||Single-year Grants|
Environmental physiology (including Physical medicine and Nutritional physiology)
|Research Institution||Hokkaido University|
HONMA Ken-ichi Hokkaido University, Graduate School of Medicine, Professor (40113625)
HONMA Sato Hokkaido University, Graduate School of Medicine, Professor (20142713)
TANAHASHI Yusuke Hokkaido University, Graduate School of Medicine, Assistant Professcr (50374228)
OHMIYA Yoshihiro Hokkaido University, Graduate School of Medicine, Professor (20223951)
NAKAMURA Tomoko Hokkaido University, Graduate School of Medicine, Assistant Professer (30451397)
白川 哲夫 北海道大学, 病院・助教授 (00187527)
安倍 博 北海道大学, 大学院・医学研究科, 講師 (80201896)
|Project Period (FY)
2003 – 2007
Completed(Fiscal Year 2007)
|Budget Amount *help
¥112,970,000 (Direct Cost : ¥86,900,000、Indirect Cost : ¥26,070,000)
Fiscal Year 2007 : ¥12,870,000 (Direct Cost : ¥9,900,000、Indirect Cost : ¥2,970,000)
Fiscal Year 2006 : ¥15,080,000 (Direct Cost : ¥11,600,000、Indirect Cost : ¥3,480,000)
Fiscal Year 2005 : ¥15,080,000 (Direct Cost : ¥11,600,000、Indirect Cost : ¥3,480,000)
Fiscal Year 2004 : ¥24,440,000 (Direct Cost : ¥18,800,000、Indirect Cost : ¥5,640,000)
Fiscal Year 2003 : ¥45,500,000 (Direct Cost : ¥35,000,000、Indirect Cost : ¥10,500,000)
|Keywords||Biological Clock / Suprachiasmatic nucleus / Clock Gene / Peripheal Clock / Molecular Oscillation / Signal Transduction / Bioluminescence / Auto-feedback loop / 分子振動系 / オートフィードバック|
The purpose of the preset study is to understand the functions of circadian clock in mammals as the multiple oscillator system from the molecular and cellular levels to behaviors.
1. Molecular mechanism of circadian system in the suprachiasmatic nucleus (SCN)
1) Cellular levels: The dynamics of the feedback loop consisting of clock genes, Per1, 2, Cry1, 2, Bmal1, and their protein product (core loop), the coupling of the Decl, Dec2 associate loop, the function of Bmal1 loop coupling with the core loop, and the output mechanism of core oscillating loop were elucidated.
2) Tissue levels: The responses of circadian rhythms in Perl, 2, Decl, Dec2 expressions to photic stimulations in the whole area of SCN and the photoperiodic responses of the circadian rhythms in Per1, 2 expressions in the whole SCN areas were elucidated.
2. Circadian oscillating system in the SCN
The circadian gene expression rhythms in the culture SCN under Tetrodotoxin treatment, the functions of circadian rhythm in the SCN
from newborn mice in which the synaptic communications are immature, the photoperiodic responses of the circadian clock gene expression rhythms in the single SCN cells
3. The circadian systems in the SCN and peripheral clocks were elucidated.
1) Behavioral levels: The circadian behavioral rhythms and the SCN and peripheral circadian systems in the histamine synthetic enzyme knockout mice, the circadian clock gene expression rhythms in the discrete areas of brain in the methamphetamine treated mice, the differences in the non-photic entrainment of the central and peripheral clocks were elucidated.
2) Tissue levels: The mechanism of Dexamethasone-induced circadian rhythm, the auto-feedback regulation in the peripheral circadian system, the responses of auto-feedback loop in the peripheral clock to the over-expression of clock gene were elucidated.
4. Introduction of a bioluminescence reporter system for clock gene expressions into mice
Transgenic mice were produced in which bioluminescence reporter system for Per1 and Bmal1 were produced. Less