AGING IN PROSIMIAN PRIMATE--MODEL FOR ALZHEIMER'S DISEASE PATHOLOGY

原猴灵长类动物的衰老——阿尔茨海默病病理学模型

• 批准号: 3802473
• 负责人: DONALD E SCHMECHEL
• 金额: --
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3802473
• 关键词: Alzheimer's disease; Ceboidea; acute phase protein; aging; amyloidosis; animal age group; animal colony; antioxidants; astrocytes; central nervous system disorders; cytokine; dietary trace element; disease /disorder model; free radicals; hemosiderosis; hypocupremia; interleukin 1; microglia; neuritic plaques; nutrition related tag

The proposed research "Aging in prosimian primate: model for AD pathology" is based on the finding that several possibly related syndromes occur during CNS aging in the prosimian primate species of Otolemur. These include: central cholinergic dystrophy, beta-amyloidosis (plaques and vascular amyloid), and central acute phase response (activated microglia and elevated interleukin-1 levels). In addition, these animals manifest spontaneously in captivity dietary iron overload syndrome and mild copper deficiency which may be associated with CNS aging pathology. The specific aims are: SPECIFIC AIM 1: To test a series of Otolemurs of various ages for the attributes of copper deficiency in peripheral tissues and CNS, and to correlate iron and copper status with abnormalities in acute phase proteins (ceruloplasmin and beta-amyloid protein), abnormality in central noradrenergic and cholinergic pathways, appearance of beta-amyloidosis (vascular and plaque), and abnormalities in central immune mechanisms (gliosis, interleukin levels, and activation of microglia). SPECIFIC AIM 2: To test whether all prosimians with DIOS have 'chronic' acute phase response and the relationship to copper deficiency; and to see whether chronic stimulation of acute phase response produces a stepwise increase in CNS injury. SPECIFIC AIM 3: To test the longterm effect of altering trace mineral balance, and of protective drug regimens to CNS injury in cohorts of young Otolemur and other prosimians followed for 4-5 years to the age where CNS injury is evident in 'normal' captive Otolemur. The goal of the proposed research is to describe the relationship between peripheral abnormalities and central nervous system aging in Otolemur. Understanding the temporal sequence and cellular basis of these aging changes may further rational prevention and treatment. Vulnerability to age-related CNS injury in Otolemur may be pertinent to mechanisms n human aging and diseases with AD pathology.

拟议的研究“ prosimian灵长类动物的衰老：AD病理模型” 是基于发现发生的几种可能相关综合症的发现 在Otolemur的Posimian灵长素种中，中枢神经系统衰老期间。 这些 包括：中央胆碱能营养不良，β-淀粉样变性（斑块和 血管淀粉样蛋白）和中央急性期反应（活化的小胶质细胞 和白介素-1水平升高）。 另外，这些动物体现了 自发圈养的饮食铁超载综合征和温和铜 可能与CNS衰老病理学有关的缺乏症。 具体 目的是： 特定目的1：测试一系列各个年龄的耳鼻肌 外周组织和中枢神经系统中铜缺乏的属性，以及 将铁和铜状态与急性期蛋白质异常相关 （Ceruloplasmin和β-淀粉样蛋白），中央异常 去甲肾上腺素和胆碱能途径，β-淀粉样变性的出现 （血管和斑块），中央免疫机制异常 （神经胶丝水平和小胶质细胞的激活）。 特定目的2：测试所有与DIO的Prosimins是否具有“慢性” 急性相反应和与铜缺乏的关系；并看到 慢性刺激急性期反应是否会逐步产生 中枢神经系统损伤的增加。 特定目标3：测试改变痕量矿物的长期效果 平衡和保护性药物方案对中枢神经系统损伤的年轻人群 奥托勒缪（Otolemur）和其他前司令官紧随其后4-5岁以下的年龄 在“正常”圈式耳瘤中，受伤是显而易见的。 拟议研究的目的是描述 耳细胞中的外周异常和中枢神经系统衰老。 了解这些衰老的时间顺序和细胞基础 变化可能会进一步预防和治疗。 脆弱性 在耳细胞中与年龄相关的中枢神经系统损伤可能与人类的机制有关 患有AD病理学的衰老和疾病。