Molecular and cellular basis of reversible hypothermia

可逆低温的分子和细胞基础

基本信息

批准号：
10583822
负责人：
Elena Gracheva
金额：
$ 51.53万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-12-05 至 2027-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10583822
关键词：
Ablation Acute Affect Animal Model Animals Arousal Blood Body Temperature Brain Brown Fat Complex Cutaneous Data Detection Development Drops Electrophysiology (science)Fiber Glean Goals Hamsters Heart Heart Arrest Hibernation Histology Homeostasis Hour Human Hypothalamic structure Ion Channel Knock-out Knowledge Laboratories Laboratory mice Lesion Maintenance Mammals Measurement Metabolism Modeling Molecular Molecular Evolution Monitor Mus Nature Nerve Tissue Neurons Orthologous Gene Output Pathologic Pathway interactions Personal Satisfaction Pharmacology Phenotype Photometry Physiologic Thermoregulation Physiological Physiology Preoptic Areas Process Respiration Role Salivary Glands Skeletal Muscle Spermophilus Squirrel Stroke Structure System Temperature Temperature Sense Testing Therapeutic Thermogenesis Tissues Trauma Visceral Work behavior test biophysical analysis biophysical properties comparative experimental study in vivo induced hypothermia insight interdisciplinary approach mutant natural hypothermia novel optogenetics pharmacologic response sensor somatosensory tool virtual

项目摘要

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.

项目摘要温度调节是一个基本过程，几乎影响动物生理的所有方面。在哺乳动物中，核心体温受到神经元的监测下丘脑。这些神经元的活性决定了驱动的神经元输出温度调节并控制体温。尽管具有基本的生理学显着性，温度稳态的分子基础在正常，适应性和病理状况仍然晦涩难懂。哺乳动物冬眠是A的周期性重编程温度调节表型。这个过程与戏剧性的生理有关扰动：心脏和呼吸率降低，核心体温从37°C降至2-- 4°C。在冬眠唤醒后，所有物理参数在数小时内返回正常。这种显着的可塑性表明，在温度调节中存在特定的适应性冬眠系统，但潜在的细胞和分子机制仍然神秘。在这个基本的科学建议中，我们将采用比较的多学科方法了解使用POA水平的可逆性低温的细胞和分子原理，使用一种新型的耐受体温动物模型，冬眠了13层的松鼠，实验室小鼠，一种非灭绝物种。了解冬眠如何实现可逆的体温过低将促进药理学的发展以诱导和调节体温过低在哺乳动物中。