7/8 NADIA U01 Recovery of Adolescent Alcohol Disruption of Basal Forebrain-Cortical Projection Circuits

7/8 NADIA U01 青少年酒精恢复对基底前脑皮质投射回路的破坏

基本信息

批准号：
10831641
负责人：
Lisa M Savage
金额：
$ 15.29万
依托单位：
STATE UNIVERSITY OF NY,BINGHAMTON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10831641
关键词：
Abstinence Acceleration Acetylcholine Acute Adolescence Adolescent Adult Alcohol consumption Alcohols Amyloid beta-Protein Binding Brain Brain Pathology Cell Death Chronic Data Science Development Educational process of instructing Equity Ethanol Exposure to Faculty Functional disorder Grant Health Hippocampus Mediating Mediator Mentors Modeling NGFR Protein Nerve Growth Factors Pathologic Phenotype Positioning Attribute Process Publications Recovery Research Research Activity Research Personnel Rodent Model Structure Training Training Support Writing adolescent alcohol exposure adolescent binge drinking alcohol exposure alcohol use disorder basal forebrain binge drinking career career development cellular pathology cholinergic cognitive function dementia risk experience gamma-Aminobutyric Acid in vivo innovation neurogenesis neuropathology novel parent project pathological aging receptor response tenure track

项目摘要

Project Summary The requested Research Supplement to Promote Diversity in Health-Related Research will support the training of an outstanding Early Investigator developing an independent research career in the field of developmental alcohol and later brain pathology. Heavy alcohol consumption during adolescence is associated with persistent changes in brain structure, connectivity, and adult hippocampal and cortical-mediated cognitive functions. Enduring pathological changes consistently observed in rodent models of adolescent ethanol exposure (Adolescent Intermittent Ethanol; AIE) include reductions of nerve growth factor, suppression of the cholinergic phenotypes, changes in activity-dependent acetylcholine release, and blunted hippocampal neurogenesis. The current Supplement to Promote Diversity extends the research scope of the Parent Project by examining whether AIE increases amyloid-β (Aβ) hippocampal levels, serving as a synergistic mediator of cellular pathology. At high levels, Aβ also binds to the p75 neurotrophin receptor, contributes to cell death, and may predispose the brain toward an accelerated pathological response. Given that pathological Aβ release is activity-dependent, a novel γ-aminobutyric-acid type-A receptor modulator (GABAAα5) will be used to correct AIE- induced Aβ dysfunction. These research activities will expand the research experiences and scientific scope of the candidate. Specifically, the research plan will expose the candidate to developmental ethanol perspectives and several innovative technical approaches (in vivo brain activity; programming, data science essentials). The mentoring plan will entail training in equitable and inclusive mentoring and teaching, effective publication and grant writing, and networking with leading researchers with expertise in developmental alcohol exposure and adult neuropathology. Critically, the candidate will be exposed to an academic model that blends teaching, mentoring, and research. Career development and mentoring plans are cohesively devised to facilitate a successful transition to a tenure-track faculty position by the candidate.

项目概要所要求的促进健康相关研究多样性的研究补充将支持培养优秀的早期研究者开展独立研究在发育性酒精和后来的脑病理学领域的职业生涯。青春期与大脑结构、连接性和功能的持续变化有关成人海马和皮质介导的认知功能。在青少年乙醇暴露的啮齿动物模型中一致观察到（青少年间歇性乙醇；AIE）包括减少神经生长因子，抑制胆碱能表型、活动依赖性乙酰胆碱释放的变化和海马钝化目前的《促进多样性补充》扩展了该研究的研究范围。家长项目通过检查 AIE 是否会增加海马淀粉样蛋白-β (Aβ) 水平，服务作为细胞病理学的协同介质，Aβ 在高水平时也与 p75 结合。神经营养素受体，导致细胞死亡，并可能使大脑倾向于加速病理反应鉴于病理 Aβ 释放是活动依赖性的，a 新型γ-氨基丁酸A型受体调节剂（GABAAα5）将用于纠正AIE- 这些研究活动将扩大研究经验并促进 Aβ 功能障碍。具体来说，研究计划将使候选人接触到的科学范围。发育乙醇的观点和几种创新的技术方法（体内大脑活动；编程、数据科学要点）。公平和包容的指导和教学，有效的出版物和资助写作，以及与在发育性酒精暴露和成人方面具有专业知识的领先研究人员建立联系至关重要的是，候选人将接触到混合的学术模型。教学、指导和研究是紧密结合的。旨在促进候选人成功过渡到终身教授职位。