AGING VULNERABILITY TO INFLAMMATORY PROCESSES

描述：拟定研究将继续研究 选择过程的性质，导致退化的变化， 阿尔茨海默病（AD）患者的大脑。AD是公认的 世界面临的主要公共卫生和生活质量问题 社区AD的特征在于一组独特的神经病理学 病变，例如老年斑，和选定的神经系统的死亡。 炎症过程在发病机制中的作用尚未明确 的AD。这些研究将调查生物化学、组织病理学和 慢性暴露于炎症因子的行为后果 正常大鼠和过度表达人类β-淀粉样蛋白的大鼠的大脑。 该项目将测试炎症过程是 参与细胞功能障碍的初始阶段， 细胞对内源性毒素的脆弱性;这些变化反过来可能 导致细胞死亡。此外，Pi将调查是否存在 与年龄相关的对这些过程的脆弱性的增加。 最后，因为导致死亡的一连串生化过程 神经元变性可能涉及NMDA受体的激活， 产生一氧化氮或洋地黄素，或激活 白细胞介素-1受体，研究还将调查它是否是 可能拮抗这些过程并提供神经保护。

DESCRIPTION: The proposed studies will continue investigations into the nature of the selection process that leads to degenerative changes in the brains of humans with Alzheimer's Disease (AD). AD is recognized is one of the major public health and quality-of-life problems facing the world community. AD is characterized by a distinct set of neuropathological lesions, e.g. senile plaques,a nd the death of selected neural systems. Inflammatory processes play an as yet undefined role in the pathogenesis of AD. The studies will investigate the biochemical, histopathological and behavioral consequence of chronic exposure to inflammatory agents within the brain of normal rats and rats that over-express human beta-amyloid. The project will test the hypothesis that inflammatory processes are involved in the initial stages of cellular dysfunction that may alter cellular vulnerability to endogenous toxins; these changes may in turn lead to cell death. In addition, the Pi will investigate whether there is an age-associated increase in the vulnerability to these processes. Finally, because the cascade of biochemical processes that leads to neuronal degeneration may involve the activation of NMDA receptors, the production of nitric oxide or prostaglandins, or the activation of interleukin-1 receptors, the studies will also investigate whether it is possible to antagonize these processes and provide neuroprotection.