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，成人心理荒地状况受早期生活质量的强烈影响关心。虐待，忽视，孤立和贫困都与较差的认知能力有关成年和衰老。此外，当前老年人的美国人口比例迅速增长步伐，到2030年将达到总人口的20％。这转化为美国的负担医疗保健系统治疗与衰老有关的认知下降。但是，这个问题可能至少部分是如果采取快速行动来识别危险的个体并创建预防性干预措施，则废除了。更好可以通过了解如何了解成年和衰老的个人记忆障碍风险调节记忆的神经系统在产后发育过程中会组装。拟议的项目是旨在了解与人类衰老相关的空间记忆障碍当这些记忆系统经历最终成熟时，重点关注大鼠的产后年龄，第三个后周结束。大鼠的这个年龄与人类空间记忆的最终成熟相似，从出生后约两到三年开始。基于寿命的研究设计采用了测定细胞，药理，系统和行为水平。更具体地说，提出的实验检查海马在海马的快速作用突触受体（AMPA受体）功能的变化与神经元功能和空间导航能力改变的突触和关系。这跨学科项目将提高我们对内存网络成熟的理解，这将有助于进来了解成年和衰老中空间记忆能力的显着变化。此外，调查结果将改善预防性措施的设计，以维持记忆，并提高有效性衰老中记忆力障碍的治疗方法。