Deborah Cory-Slechta

 

Epidemiological studies have now associated air pollution (AP) exposures with multiple neurodevelopmental disorders (NDDs), including autism spectrum disorder, schizophrenia and attention deficit hyperactivity disorder. While each of these NDDs has unique features, they also share multiple characteristics, including a male-bias, which are replicated in our studies in mice of early postnatal (human 3rd trimester brain development equivalent) exposures to concentrated ambient ultrafine particles (UFPs), considered the most reactive component of AP. Exposures of mice to from postnatal days 4-7 and 10-13, considered equivalent to human third trimester brain development produce persistent changes, including ventriculomegaly (enlarged lateral ventricles), microglial activation, elevated glutamate levels, reduction in size and myelination of the corpus callosum as well as nucleus accumbens cell death; behavioral features have included impairments in social behaviors and increased impulsivity. Collectively these findings provide biological plausibility for the epidemiological associations of AP with NDDs. These developmental UFP exposures also resulted in marked elevations of metals and trace elements in brain, including iron, copper and aluminum, an effect consistent with brain metal dyshomeostasis, which impairs brain development and function. Consequently, we have begun to assess the extent to which iron (Fe) nanoparticle inhalation can phenocopy UFP effects. To date, our studies show that Fe produces ventriculomegaly, astrocytic activation and marked changes in striatal neurochemistry in both sexes, albeit generally in opposite directions, along with nucleus accumbens cell death in males. A role of AP-induced brain trace metal dyshomeostasis in these NDDs could also underlie the heterogeneity of NDDs, as metal content of AP will differ by time, geography, climate, etc during pregnancy and after birth. Economic and social costs of NDDs impose a significant burden. Collectively, these findings suggest that AP could be a broad risk factor for NDDs and thus understanding component(s) of AP that underlie these effects is critical to understanding mechanisms, defining potential intervention strategies and protecting public health via AP regulation.

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 Dr. Deborah Cory-Slechta is a Professor of Environmental Medicine, Pediatrics and Public Health Sciences at the University of Rochester Medical School, and former Chair of its Department of Environmental Medicine and PI of its NIEHS Core Center Grant. She also previously served as Dean for Research at the University of Rochester Medical School, and as Director of the Environmental and Occupational Health Sciences Institute of Rutgers University. Her research, which has resulted in over 200 peer-reviewed publications to date includes both animal models and human studies focused largely on the consequences of developmental exposures to environmental chemicals on brain development and behavior. Her earlier work examined the effects of developmental exposures to metals and pesticides in animal models and human cohorts. Over the past 10 years she has undertaken studies of the impact of air pollution on brain development and behavior, with exposures to concentrated ambient ultrafine particles that have led to 20 peer-review publications. Dr. Cory-Slechta has served on advisory panels of the NIH, the FDA, the Environmental Protection Agency, the National Academy of Sciences, the Institute of Medicine, and the Agency for Toxic Substances and Disease Registry, and on the editorial boards of the journals Environmental Health Perspectives, Neurotoxicology, Toxicology, Toxicological Sciences, Toxicology and Applied Pharmacology and Neurotoxicology and Teratology. She also served on the Board of Scientific Counselors, ATSDR/CDC. In 2017, she was the recipient of the Distinguished Neurotoxicologist Award from the Neurotoxicology Specialty Section of the Society of Toxicology. In 2021, she was the recipient of the Distinguished Toxicology Scholar Award from the Society of Toxicology.