EXCITATORY AMINO ACIDS IN THE AGING BRAIN

衰老大脑中的兴奋性氨基酸

• 批准号: 3084899
• 负责人: KATHY R MAGNUSSON
• 金额: $ 5.85万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-11-01 至 1991-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3084899
• 关键词: aminoacid; aspartate; basal ganglia; brain mapping; cerebral cortex; glutamate receptor; glutamates; high performance liquid chromatography; hippocampus; human tissue; laboratory rat; monoclonal antibody; neurotoxins; neurotransmitters

The long term goal of this research is to investigate age-related changes in the concentrations of excitatory amino acids and in the number and/or affinities of receptors which utilize them as putative neurotransmitters. The process of aging involves a loss of degeneration of neurons and their processes in certain vulnerable brain areas. These pathologic changes are also seen in Alzheimer's disease. However, the severity of degeneration and the extent of brain areas affected are much greater with Alzheimer's disease. Excitatory amino acids have been shown to act as neurotoxins when in excess, such as in hypoxic episodes. They have also been implicated as neurotransmitters of axons which are presynaptic to cholinergic neurons located in areas most affected by aging pathology. The following proposal is based on the hypothesis that excitatory amino acids may act as neurotoxins in the aging process. The proposed investigation is described by the following five specific aims: 1) To determine age-related changes in excitatory amino acid concentration in whole brain and in brain extracellular fluid using HPLC techniques. 2) To analyze the distribution of neurons utilizing glutamate of aspartate within the nucleus basalis, hippocampus and cerebral cortex utilizing monoclonal antibodies and immunohistochemistry. 3) To ascertain the origin of glutamatergic or aspartatergic input to age-affected brain regions using combined retrograde transport-immunohistochemical techniques. 4) To determine possible age-related changes in the number and/or affinity of glutamate receptor binding sites using in vitro receptor autoradiographic techniques. 5) To detemine age-related changes in whole brain concentrations of amino acids and possibly in glutamate binding sites in human autopsy tissue. The results obtained will provide data concerning possible changes in concentrations of excitatory amino acids and their receptors during aging and basic information on the distribution and projections of excitatory amino acid neurons in cerebral cortex, hippocampus and nucleus basalis.

这项研究的长期目标是调查与年龄有关的变化 兴奋性氨基酸的浓度和数量和/或 受体的亲和力，利用它们作为假定的神经递质。 衰老的过程涉及神经元的变性丧失及其 在某些脆弱的大脑区域。 这些病理变化是 也见于阿尔茨海默病。 然而，退化的严重程度 而阿尔茨海默氏症患者大脑受影响的区域更大 疾病 兴奋性氨基酸已被证明是神经毒素， 过量，例如在缺氧发作时。 他们也被牵连， 突触前胆碱能神经元轴突的神经递质 位于最受衰老病理影响的区域。 了以下案文 是基于兴奋性氨基酸可能作为 衰老过程中的神经毒素 建议的调查描述 通过以下五个具体目标： 1)确定兴奋性氨基酸浓度的年龄相关变化 全脑和脑细胞外液中的含量。 2)分析利用谷氨酸或天冬氨酸的神经元的分布 在基底核、海马和大脑皮层内， 单克隆抗体和免疫组织化学。 3)为了确定神经元或突触神经元输入的来源， 年龄影响的大脑区域， 转运免疫组织化学技术。 4)为了确定可能与年龄相关的数量和/或亲和力变化， 谷氨酸受体结合位点的研究 放射自显影技术。 5)为了测定全脑氨基甲酸浓度的年龄相关变化， 酸和可能在人体尸检组织中的谷氨酸结合位点。 所获得的结果将提供有关可能的变化的数据， 衰老过程中兴奋性氨基酸及其受体的浓度 和兴奋性神经元的分布和投射的基本信息 大脑皮层、海马和基底核的氨基酸神经元。