The Role of Diet-induced Obesity in Cognitive Impairment

描述（由申请人提供）：卡特丽娜·罗宾逊博士的天赋和对成功的承诺一直通过学术、跨学科成就和志愿服务得到体现。她于2004年以优异成绩毕业于阿拉巴马州奥本市奥本大学，获得实验室技术/医疗技术学士学位，并取得了许多学术成就。她在奥本大学（Auburn University）的研究生生涯中继续表现出学术卓越，在那里她获得了三个不同的“年度杰出研究生”奖。2007年，她成为第一位获得奥本大学药理学和毒理学专业药学博士学位的非裔美国女性。在2008年1月作为研究员加入伊娃·费尔德曼博士的实验室后，罗宾逊博士迅速成为科学团队中重要而富有成效的成员。她获得了竞争激烈的神经病学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。总的来说，在她的研究生和学术生涯中，罗宾逊博士发表了11篇手稿，其中包括一本书的章节，另外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（University of Michigan）神经内科研究研究员。她的不断成功和进步证明了她决心成为一名成功的独立调查员。密歇根大学为罗宾逊博士提供了一个良好的环境，使他成为一名独立的研究者。密歇根大学医学院的神经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领域的多学科环境将促进合作、协作、生产力和全面的重点研究计划。此外，罗宾逊博士、费尔德曼博士、墨菲博士和她的职业委员会之间的紧密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。研究计划肥胖增加认知障碍的风险。鉴于肥胖和认知障碍在美国都是流行病，了解将两者联系在一起的机制是必要的。研究表明，改善中枢神经系统（CNS）的胰岛素信号传导对认知有积极影响；然而，肥胖个体被排除在此类研究之外。这可能是由于缺乏对肥胖和中枢神经系统中胰岛素信号之间关系的认识。第一个目的是评估肥胖对海马体中胰岛素信号的影响。我们假设中枢神经系统胰岛素抵抗是导致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起作用，但尚不清楚肥胖诱导的中枢神经系统影响是否可逆。随着肥胖儿童和成人人口继续老龄化，制定有效战略以防止这一人口中的公共卫生危机非常重要。因此，本研究的第二个目的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改变会产生长期的后果，不能通过饮食干预来克服。总之，拟议研究中的发现将通过弥合肥胖和认知障碍之间的差距，对该领域产生巨大影响。这份提案对于促进Dr. Robinson的职业发展和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，专注于将代谢综合征与阿尔茨海默病的发病和进展联系起来。这个K01职业发展奖将为她提供发展技能的基础，成为神经科学社区的专家和富有成效的成员。具体来说，罗宾逊博士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，这些将为神经变性、肥胖、出版和获得资金以及项目管理奠定坚实的基础。该项目将由来自密歇根大学多个部门的热情和支持的指导团队监督。罗宾逊博士将从这群导师和顾问那里获得的专业知识，将被证明对她成长为一名年轻的独立神经科学家至关重要。

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.