Aging and sensitivity to traffic-generated air pollutants in male and female mice

描述（由申请人提供）：化石燃料产生的空气污染物被认为会加速动脉和肺部疾病。此外，通过对年轻人的尸检（Block & Calderon-Garciduenas 2009）和对中年人的流行病学研究（Chen & Schwartz 2009）发现，发育和衰老过程中的脑功能障碍与空气污染物有关。相应地，幼龄啮齿动物在暴露于交通产生的纳米PM （nPM）后会出现神经胶质炎症变化（Zanchi et al . 2010; Kleinman et al . 2008）。我们的实验数据显示了nPM在体内和体外对神经元谷氨酸能受体的影响。我们建议分析年龄和性别在年轻成年和中年C57BL/6小鼠中nPM神经退行性作用的相互作用，使用来自洛杉矶城市的再雾化nPM。目的1将动物暴露于再雾化的nPM 20周，评估记忆、神经元和神经胶质功能。目的2将评估体外胶质细胞年龄对nPM水悬液对神经元活动的影响。

DESCRIPTION (provided by applicant): Air pollutants derived from fossil fuels are recognized for accelerating arterial and pulmonary diseases. Moreover, brain dysfunctions during development and aging have been associated with air pollutants by postmortem findings on young humans (Block & Calderon-Garciduenas 2009) and by epidemiologic studies of the middle-aged (Chen & Schwartz 2009). Correspondingly, young rodents show glial inflammatory changes with defined exposure to traffic-generated nano-sized PM (nPM) (Zanchi et al 2010; Kleinman et al 2008). Our pilot data show effects of nPM on neuronal glutamatergic receptors in vivo and in vitro. We propose to analyze age and gender interactions in neurodegenerative effects of nPM in young adult and middle-aged C57BL/6 mice, using re-aerosolized nPM from urban Los Angeles. Aim 1 will expose animals to re-aerosolized nPM for 20 weeks, with assessment of memory, and neuronal and glial functions. Aim 2 will evaluate in vitro glial age effects on neuronal activities in response to aqueous suspensions of nPM. PUBLIC HEALTH RELEVANCE: These novel studies will use mouse models to define the neurodegenerative pathways of urban airborne nano-sized particulate matter (nPM). We will evaluate the hypothesis that nPM causes neural damage through shared pathways of inflammation and oxidative stress. Identification of mechanisms and of relevant biomarkers in nPM toxicology is essential for development of broad-spectrum interventions.