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: 8925161
• 负责人: Catrina Sims Robinson
• 金额: $ 20.6万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8925161
• 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; receptor; response; skills; success; symposium; synaptic function; therapy development

DESCRIPTION (provided by applicant): 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 Bio gerontology 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.

描述（由申请人提供）：卡特里娜·罗宾逊博士的才能和对成功的承诺一直通过学术界、跨学科成就和志愿服务得到体现。她以优异的成绩毕业并获得学士学位。 2004年获得阿拉巴马州奥本大学实验室技术/医疗技术博士学位，取得了众多学术成就。罗宾逊博士在奥本大学的研究生生涯中继续展现了卓越的学术成就，在那里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。 Robinson 博士于 2007 年获得奥本大学药学博士学位，主修药理学和毒理学。2008 年 1 月作为研究员加入 Eva Feldman 博士的实验室后，Robinson 博士很快成为科学团队中重要且富有成效的成员。她获得了竞争激烈的神经学 T32 培训补助金的 1 年职位，然后获得了生物老年学 T32 培训补助金的 2 年职位。总体而言，罗宾逊博士在其研究生和学术生涯中发表了 11 篇手稿，其中包括一本书章节，另外还有一篇第一作者手稿目前正在审查中。 Robinson 博士于 2011 年 11 月晋升为密歇根大学神经病学系研究研究员。她持续的成功和进步证明了她成为一名成功的独立研究者的决心。环境 密歇根大学为罗宾逊博士提供了一个优秀的环境，使他能够成为一名独立研究者并取得优异的成绩。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。密歇根大学神经科学界的多学科环境将促进合作、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、墨菲博士及其职业委员会之间的密切合作构成了罗宾逊博士科学培训的核心，并将为她提供必要的职业指导以确保成功。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在美国都很流行，因此有必要了解将两者联系在一起的机制。研究表明，改善中枢神经系统 (CNS) 中的胰岛素信号传导对认知具有积极影响；然而，肥胖者被排除在此类研究之外。这可能是由于缺乏对肥胖与中枢神经系统胰岛素信号传导之间相关性的了解。第一个目的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胰岛素水平降低的主要因素。此外，虽然已经确定胰岛素在海马突触可塑性和认知中发挥作用，但尚不清楚肥胖引起的中枢神经系统影响是否可逆。随着肥胖儿童和成人人口持续老龄化，制定有效的策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，突触和认知的变化将产生长期的后果，而饮食干预无法克服这种后果。总之，拟议研究的结果将通过缩小肥胖和认知障碍之间的差距对该领域产生巨大影响。职业目标和职业发展计划本提案对于促进Robinson博士的职业发展以及为她的实验室奠定研究基础至关重要。她的目标是成为一名训练有素的独立研究者，重点关注代谢综合征与阿尔茨海默病的发病和进展之间的联系。 K01 职业发展奖将为她发展成为神经科学界专家和富有成效的成员的技能奠定基础。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经验的综合计划，这将为神经退行性疾病、肥胖、出版和获得资金以及项目管理奠定坚实的基础。该计划将由来自密歇根大学多个系的热情且支持的指导团队监督。事实证明，罗宾逊博士将从导师和顾问团队中获得的专业知识对于她成长为一名年轻的独立神经科学家至关重要。