1091. Exposure to Nanoparticulate Matter Causes White Matter Damage and Microglia Activation in Mouse Model

Authors: Michelle Connor; Kristina Shkirkova; Krista Lamorie-Foote; Arati Patel; Qinghai Liu; Todd Morgan; Constantinos Sioutas; Caleb Finch; William Mack (Los Angeles, CA)

Introduction: Exposure to air pollution, specifically particulate matter (PM), has been associated with neurocognitive decline. The pathophysiology by which this occurs may be through a neuroinflammatory state resulting in small vessel ischemic disease and white matter damage. The aim of this study was to characterize this white matter injury and examine the activation of microglia in response to PM exposure. Methods: Nanoparticulate matter (nPM, <200nm) was collected from near an urban Los Angeles freeway. Mice were exposed to re-aerosolized nPM (n=8) or filtered air (n=8) five hours/day, three days/week, for ten weeks (150 cumulative hours), and then sacrificed. Immunohistochemistry was performed to assess for white matter damage using myelin associated glycoprotein (MAG) and degraded myelin basic protein (dMBP). Microglial activation was characterized by Iba-1 staining in the corpus callosum. The cell body to dendritic process size ratio was used to quantify reactive microglia. Results: White matter injury was evident in the corpus callosum region of nPM-exposed mice. MAG integrated density was significantly decreased [p<0.001] and dMBP integrated density was significantly increased [p<0.001] in the corpus callosum of mice exposed to nPM compared to those exposed to filtered air. Iba-1 integrated density was significantly increased [p<0.05] in the corpus callosum of mice exposed to nPM compared to filtered air. Microglial cell body size to dendritic process size ratio was significantly greater [p<0.001] in the corpus callosum of mice exposed to nPM compared to filtered air. Conclusion: nPM exposure results in white matter damage and microglial activation in the corpus callosum. This data suggests that inflammation, and particularly the response of resident microglia, may be a critical mediator of white matter injury following particulate matter exposure.