PHARMACOLOGICAL CORRELATES OF AGING AND BRAIN CELL GRAFTS

项目4旨在从一个特定神经元的角度探索与年龄相关的神经退行性变 群，即蓝斑去甲肾上腺素能神经元。这个神经元群体 在正常衰老期间，大脑会恶化，阿尔茨海默氏症和帕金森氏病的大脑也会恶化 病人。LC-NE神经元的活动可能作为一种内源性保护作用，以抵御诸如 神经炎症和氧化应激。因此，本课题旨在研究蓝斑在脑内的作用。 在衰老过程中保持边缘系统和黑质纹状体系统的整体健康。自内在以来 我们认为，在完整的动物中，很难描述影响神经变性的外部因素与影响神经退化的外部因素之间的关系。 应用LC-NE神经元联合海马区和中脑区的眼内移植 黑质多巴胺神经元，以检测这些神经元在衰老和年龄相关中的特定功能 神经退行性变。内在因素和外在因素也将通过蓝莓饮食(BB)在 与项目1合作，探索其神经保护特性的机制。我们建议 根据项目4的两个假设：1)LC-NE神经元在保护其他脑区免受 氧化应激和/或炎症，以及与年龄相关的神经元变性导致继发性 海马体和中脑黑质区域受损。2)蓝莓提取物可以逆转 与年龄相关的LC-NE系统的退化，并提高移植到老龄宿主的存活率。 基于这些假设，我们制定了三个目标，在这些目标中，我们将探索两者之间的关系 LC-NE神经支配与年龄相关的炎症和氧化应激标志物之间的关系。项目4将 在蓝莓研究方面与项目1合作，在小胶质细胞标记物方面与项目2合作， 项目3在M1/M2特异性标记方面，与项目5在蛋白质水平比较方面 随着年龄的增长，神经退行性变的关键标志物有mRNA的表达。

Project 4 aims to explore age-related neurodegeneration from the perspective of one particular neuronal population, namely the locus coeruleus noradrenergic (LC-NE) neurons. This neuronal population deteriorates in the brain during normal aging but also in the brain of Alzheimer's and Parkinson's disease patients. The activity of LC-NE neurons may act as an endogenous protection against insults such as neuroinflammation and oxidative stress. Therefore this project aims to study the role of locus coeruleus in maintaining the overall health of the limbic system and the nigrostriatal system during aging. Since intrinsic vs. extrinsic factors influencing neurodegeneration are difficult to delineate in the intact animal, we propose to utilize intraocular transplants consisting of LC-NE neurons in combination with hippocampal and midbrain nigra dopamine neurons, to examine the specific function of these neurons in aging and age-related neurodegeneration. Intrinsic vs. extrinsic factors will also be examined with blueberry diets (BB) in collaboration with Project 1, to explore the mechanism for its neuroprotective properties. We propose the following two hypotheses for Project 4: 1) LC-NE neurons play a role in protecting other brain regions from oxidative stress and/or inflammation, and age-related degeneration of these neurons leads to secondary damage in the hippocampus, and the midbrain nigra region. 2) Treatment with blueberry extract can reverse age-related degeneration of the LC-NE system, and improve graft survival into the aged host. Based on these hypotheses, we have formulated three aims in which we will explore the relationship between LC-NE innervation and age-related inflammatory and oxidative stress markers. Project 4 will collaborate with Project 1 in terms of blueberry studies, with Project 2 in terms of microglial markers, with Project 3 in terms of the M1/M2 specific markers, and with Project 5 in terms of comparison of protein levels with mRNA expression for critical markers of neurodegeneration with aging.