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Enhanced Sympathoexcitation and Inactivity: Role of NMDA Neuroplasticity in RVLM

交感神经兴奋和不活动增强：NMDA 神经可塑性在 RVLM 中的作用

基本信息

批准号：
8708189
负责人：
Nicholas Ara Mischel
金额：
$ 4.12万
依托单位：
WAYNE STATE UNIVERSITY
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：
2010-08-25 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8708189
关键词：
Address Affect Animal Disease Models Animals Blood Pressure Brain Brain Stem Brain region Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Cause of Death Control Groups Data Development Disease Exhibits Experimental Designs Glutamate Receptor Goals Health Hypertension Individual Knowledge Laboratories Lead Life Style Mediating N-Methyl-D-Aspartate Receptors N-Methylaspartate National Heart, Lung, and Blood Institute Nerve Neuraxis Neuronal Plasticity Neurons Obesity Output Physical activity Physiological Prevention Public Health Publishing Rattus Reflex action Regulation Relative (related person)Research Research Proposals Risk Factors Role Societies Sympathetic Nervous System Testing Time Training United States Up-Regulation Work base blood pressure regulation cognitive function innovation response sedentary

项目摘要

DESCRIPTION (provided by applicant): Physical inactivity is a major risk factor for cardiovascular disease, the leading cause of death in the United States. Several inactivity-related cardiovascular diseases such as obesity and hypertension are characterized by increased blood pressure and activity of the sympathetic nervous system. The sympathetic nervous system is primarily controlled by an important brain region known as the rostral ventrolateral medulla (RVLM). Despite increasing rates of physical inactivity and cardiovascular disease in our society, there is very little known about how this brain region changes over time in individuals that are physically active versus those that remain sedentary. This lack of knowledge about how physical inactivity may contribute to cardiovascular disease by effects on this important brain region represents a fundamental gap in our field. This research proposal will study the changes that occur over time in regulation of the cardiovascular system by the RVLM in sedentary versus physically active animals. Recent data from the Sponsor's laboratory has shown that the response to activation of the RVLM is enhanced in sedentary relative to physically active animals. Over activity of the RVLM could be a key contributor to the overall elevation in sympathetic nervous system activity that is seen in many cardiovascular diseases. The central hypothesis of this proposal is that physical inactivity enhances, and physical activity reduces sympathetic activation produced by the RVLM. This central hypothesis is based on strong preliminary and published data from the Sponsor's laboratory. This project will determine central nervous system mechanisms by which a sedentary lifestyle may contribute to cardiovascular disease. This proposal utilizes an experimental design that will examine time-dependent changes that occur under sedentary conditions. Active animals will be considered the "healthy" control, and sedentary animals the disease model. As a whole, this proposal addresses a fundamental question regarding the effect of physical inactivity on regulation of sympathetic nervous system activity by the brain stem and is a key step in understanding the contribution of physical inactivity to cardiovascular disease.

描述（由申请人提供）：缺乏身体活动是心血管疾病的主要危险因素，而心血管疾病是美国的主要死亡原因。一些与缺乏活动相关的心血管疾病，例如肥胖和高血压，其特征是血压升高和交感神经系统活动增加。交感神经系统主要由称为头端腹外侧延髓（RVLM）的重要大脑区域控制。尽管我们社会中缺乏身体活动和心血管疾病的比例不断增加，但人们对经常活动的人与久坐的人的大脑区域如何随时间变化的情况知之甚少。对于缺乏身体活动如何通过影响这一重要的大脑区域而导致心血管疾病缺乏了解，这代表了我们领域的根本差距。本研究计划将研究久坐动物与体力活动动物中 RVLM 对心血管系统的调节随时间的变化。申办方实验室的最新数据表明，相对于体力活跃的动物，久坐的动物对 RVLM 激活的反应增强。 RVLM 的过度活动可能是许多心血管疾病中交感神经系统活动总体升高的关键因素。该提议的中心假设是，身体不活动会增强 RVLM 产生的交感神经激活，而身体活动会减少 RVLM 产生的交感神经激活。这一中心假设基于申办者实验室强有力的初步和已发表的数据。该项目将确定久坐生活方式可能导致心血管疾病的中枢神经系统机制。该提案采用了一种实验设计，将检查久坐条件下发生的时间依赖性变化。活跃的动物将被视为“健康”对照，而久坐的动物将被视为疾病模型。总的来说，该提案解决了一个基本问题，即缺乏身体活动对脑干调节交感神经系统活动的影响，并且是理解缺乏身体活动对心血管疾病影响的关键一步。