Rapid Estrogen Signaling in Brain Circuits that Guide Complex Behavior

大脑回路中快速的雌激素信号传导指导复杂的行为

基本信息

批准号：
8696245
负责人：
LUKE R REMAGE-HEALEY
金额：
$ 33.28万
依托单位：
UNIVERSITY OF MASSACHUSETTS AMHERST
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8696245
关键词：
Accounting Acute Address Adverse effects Agonist Alzheimer&apos s Disease Animals Auditory Behavior Behavior assessment Behavioral Biomedical Research Blood Circulation Brain Brain Diseases Brain Injuries Brain region Clinical Clinical Treatment Cognition Disorders Complex Coupled Data Development Discrimination Disease Progression Dose Estrogen Therapy Estrogens Event Functional disorder Genetic Transcription Goals Human Impaired cognition Link Measures Membrane Memory Methods Microdialysis Mission Neural Pathways Neuraxis Neurons Outcome Parkinson Disease Parkinson&apos s Dementia Patients Perception Pharmaceutical Preparations Positioning Attribute Prevention Production Property Prosencephalon Public Health Recovery Regulator Genes Research Resolution Sensory Signal Pathway Signal Transduction Signaling Molecule Stimulus Stroke Synaptic plasticity System Testing Time Translating United States National Institutes of Health Work awake cognitive function compliance behavior design extracellular in vivo interest medication compliance nervous system disorder neural circuit novel therapeutics programs public health relevance receptor relating to nervous system steroid hormone success therapy design transmission process treatment strategy

项目摘要

PROJECT SUMMARY Estrogens are a class of steroid hormones that can aid recovery from brain injury and reduce the impact of certain neurological disorders. Recently, the central nervous system of humans and other animals has been shown capable of generating its own local supply of estrogens, providing new opportunities for the targeted treatment of brain diseases. Historically, the clinical use of estrogens has produced mixed success, possibly because estrogenic drug treatments are designed to mimic long term actions of estrogens (days-weeks) whereas cognitive function may depend critically on the short-term actions of estrogens (seconds-minutes). Indeed, treating neurological disorders with systemic doses of estrogens is associated with adverse side effects and reduced patient compliance. The goal of this research program is to characterize the mechanisms for rapid estrogen production and action ('rapid estrogen signaling') within discrete brain regions, and to understand the consequences of these events for sensorimotor integration and behavior. Taking advantage of recent methodological advances, these studies will combine sensitive real-time measures of brain estrogen concentrations, acute recordings of identified neurons, and contemporary behavioral assessments to understand the functional significance of rapid estrogen signaling in brain circuits. This work will address a fundamental gap in our understanding of how estrogen production within the brain guides complex behavior, and will ultimately inform the development of highly-targeted estrogen therapies for cognitive and neurological disorders.

项目概要雌激素是一类类固醇激素，可以帮助脑损伤恢复并减少脑损伤的影响某些神经系统疾病。近年来，人类和其他动物的中枢神经系统已被显示出能够产生自己的本地雌激素供应，为目标人群提供新的机会治疗脑部疾病。从历史上看，雌激素的临床应用取得了不同程度的成功，可能因为雌激素药物治疗旨在模仿雌激素的长期作用（数天至数周）而认知功能可能主要取决于雌激素的短期作用（秒-分钟）。事实上，用全身剂量的雌激素治疗神经系统疾病会带来副作用。影响并降低患者的依从性。该研究计划的目标是表征机制在离散的大脑区域内快速产生雌激素并发挥作用（“快速雌激素信号传导”），并了解这些事件对感觉运动整合和行为的影响。利用最近的方法学进展，这些研究将结合大脑雌激素的敏感实时测量浓度、已识别神经元的急性记录以及当代行为评估了解大脑回路中快速雌激素信号传导的功能意义。这项工作将解决一个我们对大脑内雌激素的产生如何引导复杂行为的理解存在根本差距，并最终为认知和神经系统的高针对性雌激素疗法的开发提供信息失调。