Molecular and cellular basis of reversible hypothermia

项目总结 体温调节是一个基本的过程，几乎影响到动物生理的各个方面。 在哺乳动物中，核心体温由视前区的神经元监测。 下丘脑。这些神经元的活动决定了驱动 体温调节和控制体温。尽管它具有基本的生理功能 正常、适应和调节条件下温度动态平衡的分子基础 病理情况仍不清楚。哺乳动物的冬眠是对一种 体温调节表型。这一过程与戏剧性的生理学有关 扰动：心跳和呼吸频率下降，核心体温从37摄氏度降至2摄氏度- 4°C从冬眠中唤醒后，所有生理参数在数小时内恢复正常。 这种显著的可塑性表明在体温调节中存在特定的适应。 冬眠者系统，但潜在的细胞和分子机制仍然是个谜。 在这个基本的科学提案中，我们将采用比较多学科的方法来 在POA水平了解可逆性低温的细胞和分子原理，使用 一种新的耐低温动物模型，冬眠十三行地松鼠，以及 实验室小鼠，一种不冬眠的物种。了解冬眠者如何实现可逆 体温过低将促进诱导和调节体温过低的药理学发展 在哺乳动物身上。

Project summary Thermoregulation is a fundamental process that affects virtually all aspects of animal physiology. In mammals, core body temperature is monitored by neurons in the preoptic area of the hypothalamus. Activity of these neurons determines the neuronal output that drives thermoregulation and controls body temperature. Despite its fundamental physiological significance, the molecular basis of temperature homeostasis under normal, adaptive and pathological conditions remains obscure. Mammalian hibernation is a cyclical reprograming of a thermoregulatory phenotype. This process is associated with dramatic physiological perturbations: heart and respiration rate decrease, core body temperature drops from 37°C to 2- 4°C. Upon arousal from hibernation, all physiological parameters return to normal within hours. This remarkable plasticity suggests the presence of specific adaptations in the thermoregulatory system of hibernators, but the underlying cellular and molecular mechanisms remain enigmatic. In this basic scientific proposal, we will employ a comparative multidisciplinary approach to understand cellular and molecular principles of reversible hypothermia at the level of POA, using a novel hypothermia-tolerant animal model, hibernating thirteen-lined ground squirrel, and laboratory mice, a non-hibernating species. Understanding how hibernators achieve reversible hypothermia will facilitate the development of pharmacology to induce and regulate hypothermia in mammals.