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

描述（由申请人提供）：来自化石燃料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发现（Block & Calderon-Garciduenas 2009）和对中年人的流行病学研究（Chen & Schwartz 2009），发育和衰老期间的脑功能障碍与空气污染物有关。相应地，年轻啮齿动物在暴露于交通产生的纳米级PM（nPM）时显示神经胶质炎症变化（Zanchi et al 2010; Kleinman et al 2008）。我们的试验数据显示了nPM在体内和体外对神经元多巴胺能受体的影响。我们建议使用来自洛杉矶城市的再雾化nPM，分析nPM对年轻成年和中年C57 BL/6小鼠神经退行性影响的年龄和性别相互作用。目标1将使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将评估在体外神经胶质年龄对神经元活动的影响，响应于水性悬浮液的nPM。

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.