Central Nervous System Consequences of Postnatal Exposure to Ultrafine Particles

Saturday, 15 February 2014
Crystal Ballroom A (Hyatt Regency Chicago)
Deborah A. Cory-Slechta , University of Rochester , Rochester, NY
Accumulating evidence suggests that air pollutants can induce inflammation and oxidative stress in the brain; epidemiological studies report associations of air pollution with impaired cognition and attention, and increased risk for autism and schizophrenia. Since early development is a period of particular vulnerability of brain to such insults, we examined changes in brain development and long-term behavioral consequences of early postnatal (PN) exposure to real-time concentrated ambient particulate matter (CAPS; ultrafine particles) for 4hr/day on PN 4-8 and 10-13, a period of significant neurogenesis and gliogenesis, in mice,  with or without an additional 4 day adult (AD) exposure  (PN55-59). Mean CAPS count across exposure approximated 200,000 particles/cm3, and mean particle mass concentration was 96.4ug/m3. Notably, PN CAPS produced lateral ventricle enlargement (ventriculomegaly) that was observed 24 hr post exposure and persisted, findings seen only in males, and sometimes accompanied by coarctation.  Ventriculomegaly has been associated with both autism and schizophrenia, and is a predictor of poor neurodevelopmental outcome. Interestingly, human studies show that males are more likely to be diagnosed with autism and earlier on-set schizophrenia, paralleling these observations of male-specific lateral ventricle dilation. AD only CAPS also produced ventriculomegaly in males. PN CAPS also reduced levels of glial fibrillary acidic protein (GFAP) immunoreactivity in corpus callosum and in hippocampus, along with persistent increases in the microglia marker IBA-1, in males, findings suggestive of glial cell loss and with ‘functional disconnectivity’, also a feature of both autism and schizophrenia. Increased GFAP was observed in females, but restricted to early time points, indicating a more transient astrocytic response to PN CAPS.  Increased levels of hippocampal glutamate, consistent with excitotoxicity, were seen in both sexes after PN CAPS. Behavioral consequences were persistent and sex-dependent. In males, where behavior was studied more extensively, CAPS impaired learning and short-term memory, increased impulsive-like behavior and reduced locomotor activity.  Deficits in learning, locomotor activity and short-term memory were also observed in females. Collectively, these findings demonstrate a vulnerability of developing brain to even low levels of air pollution, particularly in males. Moreover, they raise the possibility that such exposures could serve as risk factors for autism and/or schizophrenia. Supported by NIH R21ES019105.