The role of diet-induced obesity in cognitive impairment

饮食引起的肥胖在认知障碍中的作用

• 批准号: 8634901
• 负责人: Catrina Sims Robinson
• 金额: $ 18.75万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-28 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8634901
• 关键词: Academia; Academic achievement; Achievement; Adult; Affect; African American; Age; Alabama; Alzheimer' s Disease; American; Aptitude; Award; Basic Science; Behavior; Blood - brain barrier anatomy; Book Chapters; Brain; Cerebrospinal Fluid; Clinical Sciences; Cognition; Cognition Disorders; Cognitive; Cognitive deficits; Collaborations; Communities; Data; Dementia; Development; Development Plans; Diet; Dietary Intervention; Disease Progression; Doctor of Philosophy; Educational workshop; Electrophysiology (science); Ensure; Environment; Epidemic; Euglycemic Clamping; Faculty; Fatty acid glycerol esters; Female; Fostering; Foundations; Funding; Genes; Gerontology; Glucose; Glucose Clamp; Goals; Grant; Health; Hippocampus (Brain); Hyperinsulinism; Impaired cognition; Impairment; Incidence; Individual; Insulin; Insulin Resistance; K-Series Research Career Programs; Knowledge; Laboratories; Lead; Learning; Link; Long-Term Potentiation; Maintenance; Manuscripts; Measures; Mediating; Medical Technology; Memory; Mentors; Metabolic; Metabolic Diseases; Metabolic syndrome; Michigan; Modeling; Monitor; Mus; Nerve Degeneration; Nervous System Physiology; Neuraxis; Neurology; Neuromuscular Diseases; Neuronal Plasticity; Neurosciences; Obesity; Onset of illness; Peripheral; Pharmacologic Substance; Pharmacology and Toxicology; Play; Population; Positioning Attribute; Prevalence; Productivity; Public Health; Publishing; Reporting; Research; Research Personnel; Risk; Rodent Model; Role; Science; Secure; Signal Transduction; Staging; Stroke; Structure; Synapses; Synaptic plasticity; Syndrome; Technology; Testing; Training; United States; Universities; Volunteerism; Weight; Work; aging population; base; behavior test; career; career development; cognitive change; cognitive function; design; economic cost; experience; graduate student; improved; in vivo; innovation; insulin sensitizing drugs; insulin signaling; medical schools; medical specialties; member; multidisciplinary; neuro-oncology; obesity in children; prevent; programs; public health relevance; receptor; response; skills; success; symposium; synaptic function; therapy development

PROJECT SUMMARY/ABSTRACT (ONE PAGE) Candidate Dr. Catrina Robinson's aptitude and commitment to succeed has been consistently exemplified through academia, interdisciplinary achievements, and volunteerism. She graduated cum laude with a B.S. degree in Laboratory Technology/Medical Technology from Auburn University, Auburn, Alabama, in 2004, with numerous academic achievements. Dr. Robinson continued to exemplify academic excellence during her graduate career at Auburn University where she received three different "Outstanding Graduate Student of the Year" awards. She was the first African American female to earn a Ph.D. in Pharmaceutical Sciences with a specialty in Pharmacology and Toxicology from Auburn University in 2007. Upon joining Dr. Eva Feldman's laboratory as a Research Fellow in January 2008, Dr. Robinson quickly became an important and productive member of the scientific team. She was awarded a 1-year position on the highly competitive Neurology T32 Training Grant and then a 2-year position of the Biogerontology T32 Training Grant. Overall, throughout her graduate and academic career, Dr. Robinson has published 11 manuscripts including one book chapter, with one additional first-author manuscript currently under review. Dr. Robinson was promoted to Research Investigator in the Neurology Department at the University of Michigan in November of 2011. Her continued success and progress attest to her determination to be a successful independent investigator. Environment The University of Michigan provides an excellent environment for Dr. Robinson to achieve and excel as an independent investigator. The Department of Neurology in the Medical School at the University of Michigan offers a vast spectrum of clinical and basic science specialties, including stroke, neuromuscular disease, neurooncology, and a cognitive disease program. The multidisciplinary environment within the neuroscience community at the University of Michigan will foster cooperation, collaboration, productivity and an overall focused research plan. Furthermore, the strong collaboration between Dr. Robinson, Dr. Feldman, Dr. Murphy, and her Career Committee forms the core of Dr. Robinson's scientific training and will provide her with the necessary career guidance to ensure success. Research Plan Obesity increases the risk for cognitive impairment. Given that both obesity and cognitive impairment are epidemics in the United States, it is imperative to understand the mechanisms linking the two together. Studies have demonstrated that improving insulin signaling in the central nervous system (CNS) has a positive impact on cognition; however, obese individuals are excluded from such studies. This is likely due to lack of knowledge of the correlation between obesity and insulin signaling in the CNS. The first aim of assesses the impact of obesity on insulin signaling in the hippocampus. We hypothesize that CNS insulin resistance is a major contributing factor to reduced levels of insulin in the CNS. Furthermore, while it has been established that insulin plays a role in hippocampal synaptic plasticity and cognition, it is not known whether obesity- induced effects in the CNS are reversible. As the population of obese children and adults continue to age, it is important to develop effective strategies to prevent a public health crisis among this population. Therefore, the second aim of the current proposal evaluates the potential long-term impact of obesity on neuroplasticity. We contend that synaptic and cognitive changes will have long-lasting consequence that cannot be overcome with dietary intervention. Together, the findings in the proposed studies will have a tremendous impact on the field by bridging the gap between obesity and cognitive impairment. Career Goals and Career Development Plan This proposal is essential to promote Dr. Robinson's career development and to lay the research foundation for her laboratory. Her goal is to become a highly trained independent investigator with a focus on linking metabolic syndrome and Alzheimer's disease onset and progression. This K01 career development award will provide the foundation for her to develop the skills to become an expert and productive member of the neuroscience community. Specifically, the career development plan outlined for Dr. Robinson consists of an integrated program of career development workshops, multidisciplinary conferences, and practical research experiences that will establish a strong foundation in neurodegeneration, obesity, publishing and securing funding, and project management. This program will be overseen by an enthusiastic and supportive mentoring team from multiple departments at the University of Michigan. The expertise that Dr. Robinson will gain from the group of mentors and consultants will prove to be vital to her development into a young independent neuroscientist.

项目摘要/摘要（一页） 候选人 卡特里娜·罗宾逊博士的才能和对成功的承诺一直体现在以下方面： 学术界、跨学科成就和志愿服务。她以优异的成绩毕业并获得学士学位。学位 2004 年，阿拉巴马州奥本大学获得实验室技术/医疗技术学位， 学术成就。罗宾逊博士在毕业期间继续展现出卓越的学术成就 在奥本大学的职业生涯中，她获得了三个不同的“年度杰出研究生” 奖项。她是第一位获得博士学位的非裔美国女性。制药科学博士 2007 年获得奥本大学药理学和毒理学专业。加入 Eva Feldman 博士的团队后 2008 年 1 月，Robinson 博士作为研究员加入实验室，很快成为一名重要且富有成效的人。 科学团队的成员。她在竞争激烈的神经病学 T32 课程中获得了为期 1 年的职位 培训补助金，然后是为期 2 年的生物老年学 T32 培训补助金职位。总的来说，她的整个 研究生和学术生涯中，Robinson 博士发表了 11 篇手稿，其中包括一本书章节， 另一份第一作者手稿目前正在审查中。罗宾逊博士晋升为研究人员 2011 年 11 月，密歇根大学神经病学系研究员。她继续 成功和进步证明了她成为一名成功的独立调查员的决心。 环境 密歇根大学为罗宾逊博士提供了一个优秀的环境，让他能够成为一名优秀的博士生 独立调查员。密歇根大学医学院神经病学系 提供广泛的临床和基础科学专业，包括中风、神经肌肉疾病、 神经肿瘤学和认知疾病项目。神经科学领域的多学科环境 密歇根大学社区将促进合作、协作、生产力和整体 重点研究计划。此外，罗宾逊博士、费尔德曼博士、 墨菲和她的职业委员会构成了罗宾逊博士科学培训的核心，并将为她提供 确保成功所需的职业指导。 研究计划 肥胖会增加认知障碍的风险。鉴于肥胖和认知障碍都是 就美国的流行病而言，了解将两者联系在一起的机制势在必行。 研究表明，改善中枢神经系统 (CNS) 中的胰岛素信号传导具有积极作用 对认知的影响；然而，肥胖者被排除在此类研究之外。这可能是由于缺乏 了解肥胖与中枢神经系统胰岛素信号传导之间的相关性。第一个目标是评估 肥胖对海马胰岛素信号传导的影响。我们假设中枢神经系统胰岛素抵抗是 中枢神经系统中胰岛素水平降低的主要因素。此外，虽然已经成立 胰岛素在海马突触可塑性和认知中发挥作用，目前尚不清楚肥胖是否 中枢神经系统中引起的影响是可逆的。随着肥胖儿童和成人人口持续老龄化， 制定有效的战略来预防这一人群的公共卫生危机非常重要。因此， 当前提案的第二个目标是评估肥胖对神经可塑性的潜在长期影响。我们 认为突触和认知变化将产生长期持续的后果，无法通过 饮食干预。总之，拟议研究的结果将对该领域产生巨大影响 通过缩小肥胖和认知障碍之间的差距。 职业目标和职业发展计划 该提案对于促进罗宾逊博士的职业发展和奠定研究基础至关重要 为她的实验室奠定了基础。她的目标是成为一名训练有素的独立调查员，重点关注 将代谢综合征与阿尔茨海默病的发病和进展联系起来。本次K01职业发展 该奖项将为她发展成为专家和富有成效的成员的技能奠定基础 神经科学界。具体来说，罗宾逊博士概述的职业发展计划包括： 职业发展研讨会、多学科会议和实践研究的综合计划 将为神经退行性疾病、肥胖、出版和安全奠定坚实的基础 资金和项目管理。该计划将由热情和支持性的指导监督 来自密歇根大学多个系的团队。罗宾逊博士将从中获得的专业知识 事实证明，导师和顾问团队对于她成长为年轻的独立人士至关重要 神经科学家。