IMMUNOLOGIC CORRELATES OF MEMORY DECLINE

记忆力下降的免疫相关性

• 批准号: 3453019
• 负责人: MICHAEL J. FORSTER
• 金额: $ 8.34万
• 依托单位: TEXAS COLLEGE OF OSTEOPATHIC MEDICINE
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3453019
• 关键词: aging; animal old age; antibody formation; autoantibody; autoimmune disorder; avoidance behavior; behavior test; behavioral habituation /sensitization; biological models; dementia; discrimination learning; escape reaction; genetic strain; hematopoietic tissue transplantation; immunization; immunofluorescence technique; laboratory mouse; longitudinal animal study; mature animal; memory disorders; psychomotor function; reflex; taste

It has been suggested that immunologic processes are involved in the etiology of these senescence-related CNS changes which are responsible for impaired cognitive function in aged individuals. This hypothesis is based partly upon evidence that humoral brain-reactive antibodies (BRA) are a correlate of cognitive dysfunction in aged humans. The purpose of the proposed studies is to test this hypothesis more directly by determining the relationship between BRA and cognitive dysfunction in animal models. One experiment is proposed to compare life-span changes in behavioral abilities of several mouse strains exhibiting heterochronic, life-span increases in BRA. Age groups of 5 selected strains will be administered various tests for learning and memory abilities. Subsequently, serum BRA of the mice will be determined by indirect immunofluorescence and by serum + complement-induced 51-Cr release from neuroblastoma. Based upon the immune hypothesis, it is expected that deteriorations in performance on the learning or memory tests by the strains will be more related to the life-span time-course of their BRA increases than to chronological age. A second experiment is proposed to test further the hypothesized relationship, through examination of BRA and behavioral abilities of young mice following their receipt of hemopoietic cells from senescent mice. It is expected that BRA formation will occur in the young mice following cell transfers, and that the time-course of BRA formation will be paralleled by deteriorations in performance on the learning or memory tests. An overall expectation is that tests designed to measure qualitatively distinguishable learning and memory abilities should yield parallel findings with normally senescent mice and young mice found to have senescent-like levels of BRA. The relationship between BRA and deterioration of sensory, motor, and reflexive processes will also be examined in the various animal models, in order that the relationship between BRA and "non-cognitive" behavioral markers of aging can be considered. The significance of these experiments is that they will indicate the potential for future studies to identify specific immunologic determinants of neurologic deterioration in aging. Should a clear relationship between BRA and cognitive dysfunction be obtained, several mouse strains will be available as models for identification of those determinants, and for the identification of therapeutic measures, chemical or nonchemical, for prevention or alleviation of senescence-related cognitive dysfunction.

有人提出，免疫过程参与 这些与衰老相关的中枢神经系统变化的病因 老年人的认知功能受损。 该假设是基于 部分是出于证据表明体液脑反应性抗体（BRA）是一种 老年人的认知功能障碍的相关性。 目的 拟议的研究是通过确定来更直接地检验该假设 动物模型中胸罩和认知功能障碍之间的关系。 提出了一个实验来比较行为的寿命变化 几种鼠标菌株的能力，表现出异性含量 胸罩增加。 将管理5个选定菌株的年龄组 各种学习和记忆能力的测试。 随后，血清胸罩 小鼠将通过间接免疫荧光和血清确定 +补体诱导的51-CR从神经母细胞瘤释放。 基于 免疫假设，可以预期 通过应变的学习或记忆测试将与 胸罩的寿命时间与年龄相比，它们的胸罩时间增加。 一个 提出了第二个实验以进一步测试假设的 通过检查胸罩和年轻的行为能力的关系 从衰老小鼠收到造血细胞后，小鼠。 它 可以预期在细胞之后的年轻小鼠中会发生胸罩 转移，胸罩形成的时间顺序将与 学习或记忆测试的性能恶化。 总体 期望的是旨在衡量可区分的测试 学习和记忆能力应以正常方式产生平行发现 衰老的小鼠和年轻小鼠发现具有衰老的胸罩水平。 胸罩与感觉，运动和变质之间的关系 反身过程也将在各种动物模型中进行检查， 命令胸罩和“非认知”行为之间的关系 可以考虑衰老的标记。 这些实验的意义 他们将表明将来的研究有可能识别 衰老中神经系统恶化的特定免疫决定因素。 胸罩和认知功能障碍之间是否存在明确的关系 获得的，将有几种鼠标菌株作为模型 确定这些决定因素，以识别 治疗措施，化学或非化学措施，用于预防或 缓解与衰老相关的认知功能障碍。