Yu-Chi Chang

Submitted by tranc4 on Mon, 08/13/2018 - 11:20

Project title: Developmental Exposure to Diesel Exhaust Causes Autism-Like Behavioral, Molecular, and Cortical Structural Alterations

Degree: PhD | Program: Environmental Toxicology (Tox) | Project type: Thesis/Dissertation
Completed in: 2018 | Faculty advisor: Lucio G. Costa


Escalating prevalence of autism spectrum disorders (ASD) in recent decades has triggered increasing efforts in understanding the role played by environmental risk factors as a way to address this widespread public health concern. Several epidemiological studies show associations between developmental exposure to traffic-related air pollution and increased ASD risk. The purpose of this project was to elucidate the neurotoxic mechanisms of developmental exposure to traffic-related air pollution in mice. A series of experiments were performed to determine whether developmental diesel exhaust (DE) exposure induces ASD-related behaviors, and whether the neuroinflammatory pathway leading to dysregulation of reelin expression was affected. C57Bl/6J mice were exposed from GD0 to PND21 to 250-300 g/m3 DE or filtered air (FA) as control. DE-exposed mice exhibited deficits in all three of the hallmark categories of ASD behavior: disrupted social interaction in the reciprocal interaction test and social preference test, disrupted social olfactory and vocal communication, and increased repetitive behavior. In brains of DE-exposed mice, increased levels of interleukin-6, increased phosphorylation of STAT3, increased expression of DNMT1, and decreased expression of reelin were found. Furthermore, cortical lamina organization was examined with immunohistochemistry staining, and subtle but significant differences in the distribution pattern of neurons expressing layer-specific markers were found. Additionally, increased PAX6, Tbr2, and Tbr1 mRNA levels were found in brains of neonatal DE- exposed mice, suggesting early promotion of the neurogenic pathway over preservation of neural progenitor cells’ self-renewal ability, which is supported by our finding of decreased adult neurogenesis in the hippocampal dentate gyrus of PND60 DE- exposed mice. Overall, these studies show that developmental DE exposure, taken as a measure of traffic-related air pollution, causes behavioral, biochemical/molecular and structural changes that resemble those present in ASD. URI