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.

项目摘要要求促进与健康相关的研究多样性的所请求的研究补充支持培训一名杰出的早期研究人员，开发一项独立研究在发育性酒精和后来的大脑病理学领域的职业。大量饮酒在青少年期间，大脑结构，连通性和成人海马和皮质介导的认知功能。持久的病理变化在青少年乙醇暴露的啮齿动物模型中始终观察到（青春期间歇性乙醇； aie）包括降低神经生长因子，抑制胆碱能表型，活动依赖性乙酰胆碱释放的变化以及钝性的海马神经发生。促进多样性的当前补充剂扩展了研究范围通过检查AIE是否增加淀粉样蛋白β（Aβ）海马水平，服务，作为细胞病理的协同介质。在高水平上，Aβ还与p75结合神经营养蛋白受体会导致细胞死亡，并可能使大脑倾向于加速病理反应。鉴于病理Aβ释放是活性依赖性的，新型的γ-氨基二酸A型受体调节剂（GABAAα5）将用于纠正AIE- 诱导的Aβ功能障碍。这些研究活动将扩大研究经验，并候选人的科学范围。具体而言，研究计划将使候选人暴露于开发人员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）。心理计划将需要进行培训公平且包容性的心理和教学，有效的出版和授予写作以及与领先的研究人员建立与发育性酒精暴露专家和成人专家的建立联系神经病理学。至关重要的是，候选人将接触到融合的学术模型教学，心理和研究。职业发展和心理计划在凝聚力上旨在促进候选人成功过渡到终身教师职位。