AGING VULNERABILITY TO INFLAMMATORY PROCESSES

描述：拟议的研究将继续调查 导致退化性变化的选择过程的本质 阿尔茨海默病(AD)患者的大脑。广告是公认的 世界面临的主要公共卫生和生活质量问题 社区。AD的特点是一套不同的神经病理。 损害，如老年斑，和选定神经系统的死亡。 炎症过程在发病机制中的作用尚不明确。 公元一代的。这些研究将调查生化、组织病理学和 人体内慢性接触炎性物质的行为后果 正常大鼠和过度表达人类β-淀粉样蛋白的大鼠的大脑。 该项目将检验炎症过程是 参与了细胞功能障碍的初始阶段，可能会改变 细胞对内源性毒素的脆弱性；这些变化可能反过来 导致细胞死亡。此外，公安局将调查是否有 这些进程的脆弱性随着年龄的增加而增加。 最后，因为生物化学过程的级联导致 神经元变性可能涉及NMDA受体的激活， 一氧化氮或前列腺素的产生，或激活 白介素1受体，这项研究还将调查它是否 有可能对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.