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Postnatal maturation: A model to study hippocampal aging and Alzheimer's disease

产后成熟：研究海马衰老和阿尔茨海默病的模型

基本信息

批准号：
9590977
负责人：
Theodore C Dumas
金额：
$ 47.1万
依托单位：
GEORGE MASON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9590977
关键词：
AMPA Receptors Adolescent Adult Age Aging Alzheimer&apos s Disease Animal Testing Animals Behavior Behavioral Biological Assay Birth Brain Brain Diseases Caring Cells Cognition Coupled Coupling Dependence Development Economics Elderly Electrophysiology (science)Environment Excitatory Synapse Glutamate Receptor Goals Growth Healthcare Systems Hippocampus (Brain)Human Impaired cognition Implant Individual Intervention Learning Life Life Experience Lighting Link Location Longevity Maintenance Malnutrition Measures Mediating Memory Memory Loss Memory impairment Modeling Molds Molecular Neurons Pathology Pattern Performance Pharmacology Phase Population Populations at Risk Poverty Predisposition Process Property Protein Subunits Proteins Psyche structure Rattus Research Research Design Retrieval Risk Running Specific qualifier value Synapses Synaptic plasticity System Task Performances Testing Training Translating abuse neglect base behavior influence cognitive ability cognitive process combat design effective intervention effective therapy emotional abuse experience experimental study improved in vivo juvenile animal memory retrieval physical abuse place fields postnatal postsynaptic prophylactic relating to nervous system response social spatial memory way finding

项目摘要

Project Summary Mounting evidence indicates that adult mental heath status is strongly influenced by the quality of early life care. Abuse, neglect, isolation, and poverty have all been associated with poorer cognitive abilities in adulthood and aging. Moreover, the proportion of the US population that is elderly currently grows at a rapid pace and will reach 20% of the total population by 2030. This translates into a troubling burden on the US health care system to treat aging-related cognitive decline. However, this problem may be at least partially abrogated if rapid action is taken to identify at-risk individuals and create prophylactic interventions. A better understanding of individual risk for memory impairment in adulthood and aging can be gained by knowing how neural systems that regulate memory are assembled during postnatal development. The proposed project is geared toward understanding the spatial memory impairments that are associated with human aging by focusing on the postnatal age in rats when these memory systems are undergoing their final maturation, the end of the third postnatal week. This age in rats parallels the final maturation of spatial memory in humans, which begins at about two to three years after birth. This lifespan-based research design employs assays at the cellular, pharmacological, systems, and behavioral levels. More specifically, the proposed experiments examine changes in the function of fast-acting synaptic glutamate receptors (AMPA receptors) at hippocampal synapses and relationships to alterations in neuronal function and spatial navigation ability. This interdisciplinary project will improve our understanding of memory network maturation, which will aid in understanding the considerable variability in spatial memory abilities in adulthood and aging. Additionally, findings will improve the design of prophylactic measures for memory maintenance and promote more effective treatments for memory impairments in aging.

项目摘要越来越多的证据表明，成年人的心理健康状况受到早期生活质量的强烈影响在乎虐待、忽视、孤立和贫困都与儿童认知能力较差有关。成年和衰老。此外，美国老年人口的比例目前正在迅速增长，到2030年将达到总人口的20%。这给美国带来了令人不安的负担医疗保健系统，以治疗与衰老有关的认知能力下降。然而，这个问题可能至少部分地如果迅速采取行动，查明高危个人并采取预防性干预措施，则可废除这一规定。更好的了解成年期和衰老期记忆障碍的个体风险可以通过了解调节记忆的神经系统在出生后的发育过程中组装。拟建项目旨在了解与人类衰老相关的空间记忆障碍，研究重点是大鼠出生后的年龄，此时这些记忆系统正在经历它们的最终成熟，产后第三周结束。大鼠的这一年龄与人类空间记忆的最终成熟相平行，在出生后两到三年开始。这项基于寿命的研究设计采用了以下检测方法：细胞、药理学、系统和行为水平。更具体地说，拟议的实验检查海马快速作用突触谷氨酸受体（AMPA受体）功能的变化突触和神经元功能和空间导航能力的改变的关系。这跨学科项目将提高我们对记忆网络成熟的理解，这将有助于了解成年和衰老过程中空间记忆能力的显著变化。此外，本发明还研究结果将改善记忆维护的预防措施的设计，并促进更有效的老年记忆障碍的治疗方法