A novel central circuit involved in paradoxical thermoregulatory inversion and induction of torpor-like state

一种涉及矛盾的温度调节反转和类似麻木状态诱导的新型中央电路

• 批准号: 9381634
• 负责人: Domenico Tupone
• 金额: $ 34.43万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-28 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9381634
• 关键词: Adenosine; Agonist; Anatomy; Animals; Area; Arousal; Brain; Brown Fat; Calcitonin Gene-Related Peptide; Characteristics; Cutaneous; Data; Dynorphins; Electrophysiology (science); Environment; Equilibrium; Exclusion; Exposure to; Fever; Generations; Heat Losses; Hibernation; Human; Hypothalamic structure; Impairment; Injection of therapeutic agent; Injury; Ischemic Stroke; Knowledge; Lead; Mammals; Mediating; Metabolism; Methods; Modeling; Muscimol; Nature; Neural Pathways; Neuraxis; Neurons; Neurotransmitters; Pathway interactions; Pharmacology; Phase; Physiologic Thermoregulation; Physiological; Play; Pontine structure; REM Sleep; RNA Interference; Rattus; Reflex action; Regulation; Research; Role; Series; Shivering; Skin; Skin Temperature; Small Interfering RNA; Stimulus; Stroke; System; Temperature; Therapeutic; Thermogenesis; Traumatic Brain Injury; Viral; Weather; awake; experimental study; falls; in vivo; natural hypothermia; neural circuit; neuronal circuitry; neurophysiology; novel; novel strategies; optogenetics; parabrachial nucleus; rapid eye movement; relating to nervous system; response; vasoconstriction

Project Summary To maintain body core temperature (TCORE) in mammals, the central nervous system thermoregulatory networks respond to skin cooling by increasing brown adipose tissue and shivering thermogenesis, and by reducing heat loss via cutaneous vasoconstriction. However, there are several conditions (e.g., hibernation, torpor, REM sleep) in which these “standard” thermoregulatory responses to protect TCORE appear to be superseded by a “thermoregulatory inversion” in which cold exposure causes inhibition of thermogenesis and warm exposure stimulates thermogenesis. We hypothesize that blockade of POA thermoregulatory function is required for the initiation of thermoregulatory inversion and that such paradoxical thermoregulation is governed by a new central thermoregulatory pathway. We will employ in vivo neurophysiological studies in anesthetized rats, a parallel demonstration of thermoregulatory inversion in a free-behaving rat model, and state-of-the-art anatomical studies to understand the relevant neural pathways regulating thermoregulatory inversion. This study will open a new field of research in thermoregulation and will elucidate a new mechanism for a rapid, controllable, stable and reversible induction of hypothermia for the treatment of ischemic stroke, brain trauma and to block persistent, high neurogenic fevers.

项目摘要 为了维持哺乳动物的体温，中枢神经系统 体温调节网络通过增加棕色脂肪组织来响应皮肤冷却， 颤抖产热，以及通过皮肤血管收缩减少热损失。然而，在这方面， 存在几个条件（例如，冬眠，麻木，快速眼动睡眠），其中这些“标准” 保护TCORE的温度调节反应似乎被“温度调节反应”所取代。 冷暴露导致产热抑制和热暴露 刺激产热。我们假设POA体温调节功能的阻断是 所需的启动温度调节逆转，这种矛盾的 体温调节由新的中枢体温调节途径控制。我们将在 在麻醉大鼠中的体内神经生理学研究， 自由行为大鼠模型中的体温调节倒置，以及最先进的解剖学研究 了解调节体温调节倒置的相关神经通路。本研究 将开辟一个新的研究领域，在体温调节，并将阐明一个新的机制， 快速、可控、稳定和可逆的诱导低温治疗缺血性心脏病 中风、脑外伤和阻断持续性神经性高热。