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.