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Investigation of hibernation marker and energy metabolism relating substances in the brain and brown fat.

大脑和棕色脂肪中冬眠标志物和能量代谢相关物质的研究。

基本信息

批准号：
14370018
负责人：
HASHIMOTO Masaaki
金额：
$ 6.53万
依托单位：
Asahikawa Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

A series of studies was carried out to investigate the physiological changes that could be an indicator for entrance and exit of the hibernation.The level of mRNA of uncoupling protein 1(UCP1 mRNA) in the brown adipose tissue (BAT), a key protein to be served as a energy balance regulator through heat production, was not changed during hibernation period in hamsters, though was in higher level compared with summer animals. We confirmed that gene expression was not newly performed during deep hibernation in the major organs, such as the heart, brain, liver, including BAT. Therefore the increased UCP1 mRNA level in deep hibernating animals is considered to be due to the enhanced production during inter-bout arousal cenothermia.BAT thermogenesis is well synchronized with control of blood supply to BAT. We clarified that endothelium type nitric oxide synthetase plays an important role in the mechanism of blood supply to BAT.BAT heat production is augmented not only by chill stress but by immobilization stress. If the immobilization stress is added repetitively in rats, adaptation will take place and thermogenic function is enhanced. In the thermogenesis enhancement, modulation of UCP1 gene expression was involved.Continuous in vivo measurement revealed that at the time of awakening from hibernation, the brain would be possibly exposed to transient oxidization stress of high level due to sudden increase in blood flow, and that is suggesting that existence of an anti-oxidization defense function.To use in telemetry of the substances relating to energy metabolism, we developed fine-wire electrode coated with enzyme containing polymer However, the sensitivity of electrode to substances in the brain was decreased concomitantly with temperature decreases during hibernation. Therefore, we used the electrode for ex vivo measurements of the samples collected from the brain by using microdialysis method, and got good results.

通过一系列的研究，探讨了反映金黄地鼠冬眠前后的生理变化。金黄地鼠的棕色脂肪组织(BAT)中解偶联蛋白1(UCP1)的mRNA水平在冬眠期间没有发生变化，但与夏季动物相比处于较高的水平。我们证实，基因表达并不是在深度冬眠期间在主要器官，如心脏，脑，肝脏，包括蝙蝠进行的。因此，深度冬眠动物中UCP1基因水平的升高被认为是由于在两轮觉醒的中心温度期间增加了产量。BAT的产热作用与对BAT的血液供应的控制很好地同步。我们阐明了内皮型一氧化氮合酶在BAT的血液供应机制中起着重要的作用。BAT的产热不仅受到冷应激的增加，而且还受到束缚应激的增加。如果在大鼠体内反复增加束缚应激，就会发生适应，生热功能增强。在生热增强中，涉及UCP1基因表达的调控。体内连续测量表明，在从冬眠中醒来时，由于血液流量的突然增加，大脑可能会暴露于高水平的瞬时氧化应激，这表明存在抗氧化防御功能。为了用于与能量代谢相关的物质的遥测，我们研制了一种涂有含酶聚合物的细丝电极，但随着冬眠期间温度的下降，电极对大脑中物质的敏感度降低。因此，我们采用微透析法将该电极用于脑组织标本的体外测量，取得了良好的效果。