Circadian Regulation of Memory

记忆的昼夜节律调节

• 批准号: 9321850
• 负责人: Geraldine J. Kress
• 金额: $ 11.92万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9321850
• 关键词: Age; Aging; Aging-Related Process; Alzheimer' s Disease; Amyloid beta-Protein; Award; Behavior; Behavioral; Biochemical; Biological Assay; Biological Clocks; Brain region; Circadian Rhythms; Clinical; Cognition; Cognition Disorders; Cognitive deficits; Collection; Cues; Disease Progression; Disease model; Electrophysiology (science); Exhibits; Funding; Gene Expression; Gene Proteins; Genetic Transcription; Goals; Grant; Hippocampus (Brain); Hour; Hypothalamic structure; Immunotherapy; Impaired cognition; Intervention; Learning; Mediating; Memory; Memory impairment; Mentored Research Scientist Development Award; Mentorship; Methods; Molecular; Molecular Profiling; Mus; Neurons; Neurosciences Research; Output; Pacemakers; Pathogenesis; Pathologic; Pathology; Periodicity; Physiological; Physiological Processes; Physiology; Process; Proteins; Regulation; Rejuvenation; Research; Research Personnel; Rodent; Role; Synapses; Synaptic plasticity; System; Testing; Time; Training; Transcriptional Regulation; age related; aged; career; career development; cognitive function; cognitive process; effective therapy; experimental study; gene function; healthy aging; improved; in vivo; innovation; memory consolidation; memory process; mouse model; neurophysiology; optogenetics; response; suprachiasmatic nucleus; synaptic function; translational neuroscience

Project Summary An NIA funded K01 Mentored Research Scientist Development Award will provide valuable training in the fields of aging and Alzheimer’s disease to facilitate my career as an independent research investigator. This grant mechanism will not only allow for critical scientific training, but also valuable career development under the mentorship of Dr. David Holtzman. During this award period, I propose to investigate the association between cognitive function and circadian rhythms during the aging process and Alzheimer’s disease (AD) progression. Cognitive decline is associated with aging and is the defining feature of AD. Circadian rhythms, which are 24-hour oscillations in behavior and physiological functions decline with age and are severely blunted with AD progression. In fact, recent studies suggest disruptions to the circadian system may occur prior to the clinical onset of memory deficits in AD. Yet, mechanisms by which the circadian system impacts cognitive processes during aging and AD pathogenesis are relatively unknown. The goal of this project is to test the hypothesis that the decay in circadian rhythmicity as observed in aging and to a greater extent in AD, causes pathological disturbances in brain regions associated with memory processing. The following aims will test this hypothesis: (1) Examine the circadian oscillation of transcriptional, biochemical, and electrophysiological processes in brain regions which support memory function in mouse models of aging and AD. (2) Examine the effects of altering circadian function on behavioral, physiological, and molecular rhythms, and if this intervention influences AD pathogenesis. The concepts and methods in this proposal are innovative and have the potential for substantially impacting our understanding for the role of circadian function on memory in aging and AD progression. Our long-term goal is to identify possible strategies to ameliorate cognitive impairments and disease progression.

项目摘要 NIA资助的K01指导研究科学家发展奖将在 衰老和阿尔茨海默氏病领域，促进我作为独立研究研究者的职业。这 赠款机制不仅允许进行严格的科学培训，而且还允许在 大卫·霍尔茨曼（David Holtzman）博士的精神训练。 在此奖项期间，我建议调查认知功能与昼夜节律之间的关联 衰老过程中的节奏和阿尔茨海默氏病（AD）进展。认知能力下降是相关的 随着衰老而是AD的定义特征。昼夜节律，行为的24小时振荡和 生理功能随着年龄的增长而下降，并因AD进展而严重钝化。实际上，最近的研究 暗示对昼夜节律系统的中断可能发生在AD中的临床记忆开始定义之前。然而， 昼夜节律在衰老和AD发病机理期间影响认知过程的机制 是相对未知的。该项目的目的是检验昼夜节律衰变的假设 正如在衰老中观察到的AD中所观察到的那样，会导致大脑区域的病理灾难 与内存处理相关联。以下目的将检验以下假设：（1）检查昼夜节律 支持支持的大脑区域的转录，生化和电生理过程的振荡 老鼠和AD的鼠标模型中的内存功能。 （2）检查改变昼夜运动对 行为，物理和分子节奏，如果这种干预影响AD发病机理。 该提案中的概念和方法具有创新性，并且有可能影响我们的 了解昼夜节律在记忆中的作用在衰老和AD进展中的作用。我们的长期目标是 确定可以改善认知障碍和疾病进展的可能策略。