Air Pollution and vulnerability to Alzheimer-like neurodegeneration in mice

描述（申请人提供）：空气污染可能加速大脑老化。对中年人的流行病学研究表明，认知能力的加速下降与空气污染的地方差异有关（Chen & Schwartz 2010），而来自高度污染的墨西哥城市的年轻人的大脑过早沉积了弥漫性淀粉样蛋白和神经胶质炎性激活，这在apoE 4携带者中更为严重（Block & Calderon-Garciduenas 2009）。相应的啮齿动物模型与交通产生的纳米尺寸的颗粒材料（nPM）的定义暴露已显示神经胶质炎症变化。我们的试验数据表明，暴露于nPM 10周激活神经胶质细胞和改变神经元nPM受体在体内和体外。我们建议分析nPM对J20-ADtg小鼠和具有更广泛的AD样神经病理学的三重转基因AD小鼠（3xTg-AD）中的神经胶质炎症、淀粉样蛋白生成和神经变性的影响。我们还将使用体外模型测试nPM促进Abeta 42产生并加剧Abeta 42诱导的毒性的假设。

DESCRIPTION (provided by applicant): Air pollution may accelerate brain aging. Epidemiological studies of the middle-age have shown accelerated cognitive decline in association with local differences in air pollution (Chen & Schwartz 2010), while brains of young adults from a highly polluted Mexican city had premature deposits of diffuse amyloid and glial inflammatory activation which were greater in apoE4 carriers (Block & Calderon-Garciduenas 2009). Corresponding rodent models with defined exposure to traffic-generated nano-sized particulate material (nPM) have shown glial inflammatory changes. Our pilot data show that exposure to nPM for 10 weeks activated glia and altered neuronal glutamatergic receptors in vivo and in vitro. We propose to analyze effects of nPM on glial inflammation, amyloidogenesis, and neurodegeneration in J20-ADtg mice and in triple transgenic AD mice (3xTg-AD), which has more extensive AD-like neuropathology. We will also test the hypotheses that nPM promotes Abeta42 production and exacerbates Abeta42-induced toxicity using in vitro models.