EXCITATORY AMINO ACID SYSTEMS IN THE AGED BRAIN

老年大脑中的兴奋性氨基酸系统

• 批准号: 3453411
• 负责人: KEVIN J ANDERSON
• 金额: $ 9.51万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-02-01 至 1996-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3453411
• 关键词: Cebidae; NMDA receptors; aging; aminoacid transport; animal old age; animal tissue; aspartate; astrocytes; autoradiography; brain injury; brain metabolism; corpus striatum; excitatory aminoacid; glutamate receptor; glutamates; high performance liquid chromatography; hippocampus; juvenile animal; male; mature animal; microdialysis; neural plasticity; neuroanatomy; neurochemistry; neuronal transport; neurons; neurotransmitters; receptor expression; synapses; synaptogenesis

Identification of the molecular and cellular events that occur in the aging central nervous system is a critical area of basic research. The state of the aging central nervous system is largely dependent on the balance between functional losses and intrinsic biological mechanisms that serve to compensate for such losses. This series of studies proposes to study excitatory amino acid (EAA) networks, because they are central to the balance between function and pathology. Dysfunction of EAA receptors would compromise learning and plasticity; their preservation would serve to maintain function; and their overactivation would promote cell death. By examining this system in models of normal aging and animal lesions, it will be possible to identify changes occurring at the level of the synapse that represent key events in plasticity mechanisms, neuronal degeneration, and normal aging. This series of experiments proposes to examine the relationship between EAA receptors and transporters in the mature and aged brain of rodents and non-human primates. Failures in one or more of these components would be expected to compromise function and perhaps contribute to the decline in cognitive abilities with aging. Some changes in the aged brain may represent plastic reactions attempting to compensate for cell loss. Such a response is observed in the young rodent brain where an entorhinal lesion causes axon sprouting and receptor plasticity in the hippocampal formation. Accordingly, receptor changes in the denervated hippocampus of mature animals will be compared with those in the aging brain. By examining each of the EAA components in the normal brain and during reactive synaptogenesis, a clearer picture of the functional and compensatory abilities of the aged brain can be derived.

鉴定发生在衰老中的分子和细胞事件 中枢神经系统是基础研究的关键领域。状态 衰老的中枢神经系统在很大程度上取决于平衡 在功能损失和服务的内在生物学机制之间 弥补此类损失。这一系列研究提出了研究 兴奋性氨基酸（EAA）网络，因为它们是 功能和病理之间的平衡。 EAA受体功能障碍将 妥协学习和可塑性；他们的保存将用于 保持功能；它们的过度活化将促进细胞死亡。经过 在正常衰老和动物病变的模型中检查该系统，它将 可以识别在突触级别发生的变化 代表可塑性机制，神经元变性和 正常衰老。 这一系列实验建议检查EAA之间的关系 啮齿动物成熟和老化的大脑中的受体和转运蛋白以及 非人类灵长类动物。其中一个或多个组件中的失败将是 期望妥协功能，也许有助于下降 衰老的认知能力。老年大脑的一些变化可能 代表试图补偿细胞损失的塑料反应。这样的 在年轻的啮齿动物大脑中观察到反应 在海马形成中引起轴突发芽和受体可塑性。 因此，受体变化的成熟海马 将动物与大脑衰老的动物进行比较。通过检查每个 正常大脑中的EAA成分和反应性期间 突触发生，更清晰的功能和补偿性图 可以得出老化大脑的能力。