Circadian rhythms and melatonin signaling in the aging gastrointestinal system

衰老胃肠系统中的昼夜节律和褪黑激素信号传导

基本信息

  • 批准号:
    8580477
  • 负责人:
  • 金额:
    $ 25.14万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-08-15 至 2017-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Biological circadian clocks are fundamental properties of all living organisms studied in any detail. In animals, clocks regulate the timing of sleep: wake cycles, as well as the coordination of internal body functions, such as temporal variations in temperature, hormone levels, aspects of disease and gastrointestinal physiology. The molecular bases for biological rhythms are at least in part regulated by the expression of "clock genes", a group of genes whose complex interactions govern 24-hour rhythms. Work in our lab has demonstrated that clock genes are important in the regulation of colonic motility: the mouse colon possesses a functional circadian clock that regulates rhythms of a wide array of genes as well as intestinal motility. Further, we have shown that the colonic clock regulates multiple downstream processes associated with normal intestinal motility, absorption, cell proliferation and cell signaling as well as potential pathological processes. In addition, in mammals, there is a hierarchical organization in which a central pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) coordinates multiple peripheral processes as well as entrains the entire system to the light: dark cycle (LD) through specialized photic pathways. Our general hypothesis is that the global regulation of gastrointestinal circadian rhythms involves the complex, bi-directional interaction of central SCN clockworks and intestinal clocks themselves, and that disruption of any of these predisposes us to disease. The overall objective of this proposal is to determine the underlying mechanism through which colonic motility varies with the time of day under normal circumstances and to determine the consequences of aging on circadian patterns of colonic motility. Our hypothesis is that one factor mediating changes in intestinal function during aging is the circadian secretion of the hormone melatonin by the pineal gland and by intestinal tissues themselves. We will therefore ask what aspects of gastrointestinal rhythms are affected by normal aging (Specific Aim 1). We will then ask whether pineal melatonin influences gastrointestinal rhythmicity in young vs aged mice at several levels of biological organization. Finally, we will ask whether interference in the production of melatonin affects aging aspects of gastrointestinal rhythmicity by comparing melatonin deficient strains of mice (C57/Bl6) with strains of mice capable of producing melatonin cycles (C3H) and whether these processes are dependent the known melatonin receptor molecules by comparing wild-type with MT1 receptor, MT2 Receptor and MT2/MT2 receptor knockout mice.
描述(由申请人提供):生物生物钟是所有生物体的基本特性。在动物体内,时钟调节着活动的时间

项目成果

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VINCENT M CASSONE其他文献

VINCENT M CASSONE的其他文献

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{{ truncateString('VINCENT M CASSONE', 18)}}的其他基金

Circadian rhythms and melatonin signaling in the aging gastrointestinal system
衰老胃肠系统中的昼夜节律和褪黑激素信号传导
  • 批准号:
    8878151
  • 财政年份:
    2013
  • 资助金额:
    $ 25.14万
  • 项目类别:
2012 Pineal Cell Biology Gordon Research ConferenceLinks to circadian clocks, sl
2012 松果体细胞生物学戈登研究会议链接到生物钟,sl
  • 批准号:
    8254269
  • 财政年份:
    2011
  • 资助金额:
    $ 25.14万
  • 项目类别:
Pacemaker Properties of the Avian Pineal Gland
鸟类松果体的起搏器特性
  • 批准号:
    7168076
  • 财政年份:
    2006
  • 资助金额:
    $ 25.14万
  • 项目类别:
COORDINATION OF CIRCADIAN PHYSIOLOGY OF DIVERSE SPECIES
不同物种昼夜生理学的协调
  • 批准号:
    6190895
  • 财政年份:
    2000
  • 资助金额:
    $ 25.14万
  • 项目类别:
COORDINATION OF CIRCADIAN PHYSIOLOGY OF DIVERSE SPECIES
不同物种昼夜生理学的协调
  • 批准号:
    6773979
  • 财政年份:
    2000
  • 资助金额:
    $ 25.14万
  • 项目类别:
COORDINATION OF CIRCADIAN PHYSIOLOGY OF DIVERSE SPECIES
不同物种昼夜生理学的协调
  • 批准号:
    6619859
  • 财政年份:
    2000
  • 资助金额:
    $ 25.14万
  • 项目类别:
Pacemaker Properties of the Avian Pineal Gland
鸟类松果体的起搏器特性
  • 批准号:
    7860595
  • 财政年份:
    2000
  • 资助金额:
    $ 25.14万
  • 项目类别:
Pacemaker Properties of the Avian Pineal Gland
鸟类松果体的起搏器特性
  • 批准号:
    7643081
  • 财政年份:
    2000
  • 资助金额:
    $ 25.14万
  • 项目类别:
Pacemaker Properties of the Avian Pineal Gland
鸟类松果体的起搏器特性
  • 批准号:
    8076774
  • 财政年份:
    2000
  • 资助金额:
    $ 25.14万
  • 项目类别:
COORDINATION OF CIRCADIAN PHYSIOLOGY OF DIVERSE SPECIES
不同物种昼夜生理学的协调
  • 批准号:
    6540208
  • 财政年份:
    2000
  • 资助金额:
    $ 25.14万
  • 项目类别:

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