Central Sympathetic Regulation of Thermogenesis in Fever

发热时交感神经中枢对产热的调节

基本信息

批准号：
8468216
负责人：
SHAUN F MORRISON
金额：
$ 33.93万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-07-15 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8468216
关键词：
Acute-Phase Reaction Address Amphetamine Abuse Anesthesia procedures Area Automobile Driving Binding Blood Vessels Blood flow Body Temperature Brain Brown Fat Cerebral Ischemia Coupled Cutaneous Dinoprostone Environment Fever Funding Goals Heart Heart Rate Heat Losses Heating Homeostasis Host Defense Hot flushes Human Hypothalamic structure Infection Invaded Investigation Life Malignant Neoplasms Mediating Mediator of activation protein Meningitis Menopause Metabolic Modeling Motor Muscle Neural Pathways Neuraxis Neurons Neurotransmitters Operative Surgical Procedures Output Pathway interactions Pattern Performance Pharmaceutical Preparations Physiologic Thermoregulation Play Population Preoptic Areas Process Production Reflex action Regulation Research Rodent Role Saliva Sepsis Septic Toxemia Shivering Skeletal Muscle Skin Spinal Stroke Sweat Sweating System Tachycardia Temperature Testing Therapeutic Thermogenesis Work base clinically significant combat defense response endogenous pyrogen expectation falls in vivo induced hypothermia insight neural circuit neuromechanism novel pathogen prostaglandin EP3 receptor prostate surgery receptor relating to nervous system response therapeutic development vasoconstriction

项目摘要

Project Summary Fever is a defended elevation in body temperature that plays a significant role in the acute phase reaction stimulated by a cascade of endogenous pyrogens released during infection. The febrile increase in body temperature is the result of a patterned autonomic and somatic motor response orchestrated by the central nervous system in response to an increased production of the pyrogenic mediator, prostaglandin E2 (PGE2), in the preoptic area (POA), a principal thermoregulatory integration center in the brain. PGE2 binding to EP3 inhibitory receptors on neurons in the POA increases core body temperature by activating neural pathways to four principal thermoregulatory effectors: increased heat production from brown adipose tissue (BAT) thermogenesis, from shivering in skeletal muscle and from a marked tachycardia and increased heat conservation through cutaneous vasoconstriction (CVC). This same constellation of responses: augmented sympathetic outflows to BAT, to the heart and to skin blood vessels and increased somatic motorneuron discharge to muscle, also constitutes the cold defense homeostatic reflex response to stimulation of cutaneous cold receptors or falls in core temperature. In the previous funding period, we have made significant progress in understanding the functional organization and neurotransmitters regulating the activity in the thermoregulatory pathways mediating the increases in BAT thermogenesis, heart rate and CVC contributing to the febrile response to PGE2 in the POA and to cold defense responses to skin cooling. We propose to extend these studies by using the fruitful in vivo electrophysiological, anatomical and neuropharmacological approaches we have perfected over the past several years to address three specific aims that will provide new and important insights into the brain mechanisms effecting fever and performing the critical homeostatic function of thermoregulation. The first aim will test the hypothesis that somatic, as well as sympathetic febrile and cold defense responses are organized through a hierarchical pathway between the POA and the medullary raphe by determining the central neural mechanism underlying the PGE2- and cold-evoked shivering response. The second aim will determine the neural basis for the fundamental differences in performance between the thermoregulatory network regulating skin blood flow and that driving BAT thermogenesis. The third aim will focus on the key integrative neurons in thermoregulation: the output neurons of the POA, to understand the mechanism for the differential control of thermoregulatory effectors and to determine their role in mediating effector responses to neurotransmitter systems implicated in conditions of thermal dysregulation.

项目摘要发烧是体温下的防御高度，在急性中起着重要作用相应在感染过程中释放出的一系列内源性金刚原。高温体温升高是图案化的自主和体细胞运动反应的结果由中枢神经系统精心策划，以响应增生的产生介体，前列腺素E2（PGE2），在原始区域（POA），主要的热调节整合中心在大脑中。 PGE2与POA中神经元上EP3抑制受体的结合增加了核心通过激活四个主要温度调节效应子的神经途径来增加体温：增加棕色脂肪组织（BAT）生热产生的热量，骨骼肌发抖和从明显的心动过速并通过皮肤血管收缩增加节能（CVC）。相同的回应星座：增强同情的流出，击球，心脏和到皮肤血管并增加了肌肉的体细胞神经元排出，也构成冷防御稳态反射反应对皮肤冷受体刺激或核心掉落的反应温度。在上一个资金期间，我们在理解功能组织和神经递质调节温度调节途径的活性介导蝙蝠的热发生，心率和CVC的增加，导致了高热反应到POA中的PGE2，以及对皮肤冷却的冷防御反应。我们建议通过使用富有成果的体内电生理学解剖学来扩展这些研究和神经药理学方法，我们在过去几年中已经完善了三个具体目的将为影响发烧的大脑机制提供新的重要见解执行温度调节的关键稳态功能。第一个目标将检验假设通过一个通过确定中心神经 PGE2和冷诱发的颤抖响应的基础机制。第二个目标将决定温度调节网络之间表现基本差异的神经基础调节皮肤血流并驱动蝙蝠的热发生。第三个目标将集中在钥匙上温度调节中的综合神经元：POA的输出神经元，以了解机制用于热调节效应子的差分控制，并确定其在中介效应器中的作用对神经递质系统的反应与热失调条件有关。

项目成果

期刊论文数量（36）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Hibernation, Hypothermia and a Possible Therapeutic "Shifted Homeostasis" Induced by Central Activation of A1 Adenosine Receptor (A1AR).

DOI：
发表时间：
2016-04
期刊：
Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology
影响因子：
0
作者：
D. Tupone;J. Cetas;S. Morrison
通讯作者：
D. Tupone;J. Cetas;S. Morrison

Highlights in basic autonomic neurosciences: central adenosine A1 receptor - the key to a hypometabolic state and therapeutic hypothermia?

基础自主神经科学亮点：中枢腺苷 A1 受体 - 低代谢状态和治疗性低温的关键？

DOI：
10.1016/j.autneu.2013.02.004
发表时间：
2013
期刊：
Autonomic neuroscience : basic & clinical
影响因子：
0
作者：
Tupone,D;Madden,CJ;Morrison,SF
通讯作者：
Morrison,SF

Rostral ventromedial periaqueductal gray: a source of inhibition of the sympathetic outflow to brown adipose tissue.

头侧腹内侧导水管周围灰质：抑制交感神经流出棕色脂肪组织的来源。

DOI：
10.1016/j.brainres.2006.01.035
发表时间：
2006
期刊：
Brain research.
影响因子：
0
作者：
Rathner,JosephA;Morrison,ShaunF
通讯作者：
Morrison,ShaunF

An orexinergic projection from perifornical hypothalamus to raphe pallidus increases rat brown adipose tissue thermogenesis.

DOI：
10.1523/jneurosci.3909-11.2011
发表时间：
2011-11-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Tupone D;Madden CJ;Cano G;Morrison SF
通讯作者：
Morrison SF

Brown adipose tissue sympathetic nerve activity is potentiated by activation of 5-hydroxytryptamine (5-HT)1A/5-HT7 receptors in the rat spinal cord.

大鼠脊髓中 5-羟色胺 (5-HT)1A/5-HT7 受体的激活可增强棕色脂肪组织交感神经活动。