Chemoanatomic changes associated with aging in vestibulo-sympathetic pathways

与前庭交感神经通路衰老相关的化学解剖学变化

基本信息

批准号：
8107476
负责人：
Gay R Holstein
金额：
$ 17.31万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-15 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8107476
关键词：
Adverse effects Age Aging Anatomy Animals Antihypertensive Agents Area Baroreflex Blood Pressure Brain Stem Cell Nucleus Chemicals Clinical Complex Data Depressed mood Disinhibition Dizziness Elderly Epinephrine Future Glutamates Goals Heart Rate High Prevalence Human Image Immunofluorescence Immunologic Label Literature Measures Mediating Modification Movement Mus Neurons Neurotransmitters Nitric Oxide Norepinephrine Nuclear Nucleus solitarius Organ Orthostatic Hypotension Outcome Pathway interactions Pattern Persons Pharmaceutical Preparations Pharmacotherapy Phenotype Physiological Population Posture Pressoreceptors Process Production Proteins Publishing Rattus Reflex action Reporting Research Reticular Formation Rodent Rodent Model Signal Transduction Site Source Stress Structure Syncope Syndrome System Tachycardia Testing Vertigo Work age effect age group age related aged base blood pressure regulation body position fall risk falls flexibility gamma-Aminobutyric Acid imidazoleacetic acid ribotide interest loss of function medial vestibular nucleus mortality nerve supply otoconia protein expression public health relevance response young adult

项目摘要

DESCRIPTION (provided by applicant): Changes in body position and posture are detected by the vestibular system and are normally accompanied by rapid modifications in blood pressure. These compensatory adjustments, which allow humans to stand up without fainting, are mediated by functional integration of the vestibular system and blood pressure control mechanisms in the caudal medullary reticular formation: signals from the vestibular otolith organs provide the primary source of input to the shorter latency vestibulo-sympathetic reflex (VSR), while arterial baroreceptors regulate sympathetic tone via the relatively long- latency baroreflex. Although the clinical literature has consistently reported a decline in vestibulo-autonomic function with age, and this decline is associated with increased risk of falling and increased mortality in older people, the cellular mechanisms underlying this loss of function are not known. The overall goal of this two-year exploratory project is to identify chemoanatomic alterations in key caudal brainstem sites of aged rodents, correlated with assessment of VSR and baroreflex function. The two specific aims are (1) to obtain physiological measures of autonomic activity, particularly heart rate and blood pressure (a) under baseline conditions, (b) in response to baroreflex activation and (c) in response to vestibular stimulation in young-adult and aged rats and mice; and (2) to visualize Fos protein, and transmitter and modulator expression in medullary regions activated by the three conditions of Aim 1, in young adult and aged rats and mice. This research will evaluate the overall hypothesis that specific alterations in the chemical anatomy of the caudal medulla parallel an age-dependent decline in VSR and baroreflex control of blood pressure. The project will also assess the utility of two common rodent models of aging for studies of vestibulo-autonomic structure and function. PUBLIC HEALTH RELEVANCE: Rapid adjustments in blood pressure normally accompany movements and changes in body position and posture; these compensatory adjustments allow humans to stand up without fainting. Orthostatic hypotension, which is highly prevalent in the elderly, occurs when the vestibulo-sympathetic reflex fails to mediate such compensatory adjustments. This project will evaluate the hypothesis that specific alterations in the chemical anatomy of the caudal medulla parallel an age-dependent decline in vestibulo-sympathetic- and baroreflex control of blood pressure, thereby suggesting new pharmacotherapies to ameliorate orthostatic hypotension and more specific anti-hypertensive medications that do not elicit disabling vestibular side effects such as dizziness and vertigo.

描述（由申请人提供）：人体位置和姿势的变化由前庭系统检测到，通常伴随着血压快速修饰。这些补偿性调整可以使人不晕而站起来，是由前庭系统和血压控制机制的功能整合所介导的：尾髓质性的网状形成：前庭耳鼻喉科器官的信号提供了向较短的延迟延迟的延迟式态度的较短的态度（VSR），同时，同步较短的态度（vsrorect），同时，vsrorectectial（VSR），同时vsrorecectial（vsrorectial），同时vsrorect conecrectial conterial recelect contrortial artorect conterial artorect anderect artorect anderect artorect。潜伏期巴罗雷弗莱克斯。尽管临床文献始终报道了与年龄的前庭自治功能下降，并且这种下降与老年人的下降风险增加和死亡率增加有关，但这种功能丧失的基础机制尚不清楚。这个为期两年的探索性项目的总体目标是确定老年啮齿动物的关键尾部脑干部位的化学解剖学改变，与评估VSR和BaroreFlex功能有关。这两个具体目的是（1）获得自主活动的生理措施，尤其是心率和血压（a）在基线条件下，（b）响应于压力反射的激活，以及（c）响应年轻人，老年大鼠和老年大鼠和小鼠的前庭刺激；（2）在年轻的成年大鼠和老年大鼠和小鼠中，在AIM 1的三个条件下激活的髓质区域中可视化FOS蛋白，以及发射器和调节剂的表达。这项研究将评估总体假设，即尾髓质的化学解剖学的特异性变化平行于VSR的年龄依赖性下降和血压的压力反射控制。该项目还将评估两个常见的啮齿动物衰老模型的效用，以研究前庭自治结构和功能。公共卫生相关性：血压的快速调整通常伴随运动以及身体位置和姿势的变化；这些补偿性调整允许人类站起来而不会晕倒。当前卫反射反射未能调解这种补偿性调整时，体位性低血压在老年人中高度普遍。该项目将评估以下假设：尾髓质的化学解剖结构的特定变化平行于年龄依赖于血压的交感神经 - 交感神经和压力反射控制，从而提出了新的药物治疗，以延应邻态性降低性降压性和更具体的抗高静态药物，并散发出较高的效果。