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.

项目概要 NIA 资助的 K01 指导研究科学家发展奖将提供宝贵的培训 衰老和阿尔茨海默病领域，以促进我作为一名独立研究人员的职业生涯。 资助机制不仅可以提供关键的科学培训，还可以提供有价值的职业发展 David Holtzman 博士的指导。 在这个奖励期间，我建议研究认知功能和昼夜节律之间的关联 衰老过程中的节律与阿尔茨海默病（AD）的进展有关。 昼夜节律是 AD 的决定性特征，即行为和行为的 24 小时波动。 事实上，最近的研究表明，生理功能会随着年龄的增长而衰退，并随着 AD 的进展而严重减弱。 表明昼夜节律系统的破坏可能发生在 AD 记忆缺陷临床发作之前。 昼夜节律系统影响衰老和 AD 发病过程中认知过程的机制 该项目的目标是检验昼夜节律衰退的假设。 正如在衰老过程中所观察到的，在更大程度上是在 AD 中观察到的，会导致大脑区域的病理紊乱 以下目标将检验这一假设：（1）检查昼夜节律。 大脑区域转录、生化和电生理过程的振荡，支持 (2) 检查改变昼夜节律功能对 行为、生理和分子节律，以及这种干预是否影响 AD 发病机制。 该提案中的概念和方法具有创新性，有可能对我们的 了解昼夜节律功能对衰老和 AD 进展中记忆的作用。 确定改善认知障碍和疾病进展的可能策略。