GALANIN PLASTICITY IN ALZHEIMER'S DISEASE

甘丙肽在阿尔茨海默病中的可塑性

• 批准号: 3123408
• 负责人: ELLIOTT Jay MUFSON
• 金额: $ 13.43万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3123408
• 关键词: Alzheimer's disease; Cebidae; Parkinson's disease; acetylcholine; aging; animal old age; cell type; cellular pathology; dementia; gene expression; growth factor receptors; histology; human tissue; immunocytochemistry; in situ hybridization; innervation; interneurons; juvenile animal; messenger RNA; monoclonal antibody; neural degeneration; neural plasticity; neuroanatomy; neuropeptides; neurotrophic factors; northern blottings; pathologic process; postmortem; prosencephalon; species difference

The overall objective of this proposal is to gain a more complete understanding of the pathologic alterations which occur between magnocellular cholinergic neurons and galanin containing interneurons and their processes within the basal forebrain of human normal aged, Alzheimer's (AD) and Parkinson's (PD) dementia individuals. Since galanin is inhibitory to acetylcholine, it has been hypothesized that hyperinnervation by galanin containing profiles upon nucleus basalis cholinergic neurons in AD and PD may play a key role in the degenerative process(es) underlying cholinergic cell dysfunction in these neurodegenerative disorders. To evaluate this hypothesis we will 1) determine the cellular location of mRNA for galanin synthesis within the human basal forebrain subfields, 2) determine whether the expression of galanin mRNA parallels the species difference between human and monkeys we reported for the peptide galanin within the basal forebrain (36), 3) determine whether other basal forebrain cell types not currently known to contain the peptide galanin express its mRNA, 40 determine whether galanin hyperinnervation to the cholinergic basal forebrain neurons occurs in all subfields of this region in Alzheimer's and Parkinson's dementia, 5) determine whether the hyperinnervation of galanin profiles within the nucleus basalis is accompanied by an over expression of galanin mRNA, and 6) determine whether the basal forebrain hypertrophic galanin containing profiles innervate ALZ-50 expressing elements. The planned studies will utilize immunohistochemistry using a polyclonal galanin antibody, an IgM mouse monoclonal ALZ-50 antibody and galanin mRNA in situ hybridization. The data generated from this proposal will provide much needed information concerning the neurodegenerative events which may play a pivotal role in basal forebrain cholinergic degeneration in Alzheimer's and Parkinson's dementias. Furthermore, these data may suggest avenues for the development of new pharmacological therapies as a means of retarding intellectual deterioration in dementia.

该提案的总体目标是获得更完整的 了解在 巨细胞胆碱能神经元和含有中间神经元的加拉宁 它们在人类正常老化的基础前脑内的过程， 阿尔茨海默氏症（AD）和帕金森（PD）痴呆症患者。 自加拉宁以来 是对乙酰胆碱的抑制作用，已经假设 galanin含有基核的特征性高温作用 AD和PD中的胆碱能神经元可能在退化中起关键作用 这些过程中的胆碱能细胞功能障碍的过程 神经退行性疾病。 为了评估这一假设，我们将1） 确定mRNA的细胞位置 人类基础前脑子场，2）确定是否表达 Galanin mRNA与人与猴子之间的物种差异相似 报道了基底前脑内的肽加拉宁（36），3） 确定当前是否已知的其他基础前脑细胞类型是 含有肽甘氨酸表达其mRNA，40确定galanin是否是 胆碱能基础前脑神经元的过度连接发生在所有人中 阿尔茨海默氏症和帕金森痴呆症的该地区的子场，5） 确定是否在葡萄蛋白轮廓的过度作用 核核伴有Galanin mRNA的过度表达，和 6）确定是否含有基础前脑肥大甘氨酸 剖面支配ALZ-50表达元素。 计划的研究将 使用多克隆甘氨酸抗体，IgM利用免疫组织化学 小鼠单克隆ALZ-50抗体和Galanin mRNA原位杂交。 该提案产生的数据将提供急需的信息 关于神经退行性事件，可能在 阿尔茨海默氏症和帕金森氏症的基础前脑胆碱能变性 痴呆症。 此外，这些数据可能建议开发途径 新的药理学疗法作为智力智力的一种手段 痴呆症恶化。