Abstracts

Erica Jansen, Ph.D., M.P.H., University of Michigan

Title: Do Toxicants Affect Adolescent Sleep? Findings From the Early Life Exposure to Environmental Toxicants (ELEMENT) Study (3MB)

Abstract: Exposure to toxicants, particularly during specific developmental periods, is known to affect neurological and cognitive outcomes. However, potential effects on sleep, also a neurological function, have rarely been assessed. In this talk, I will discuss recent findings on links between toxicants and sleep outcomes in adolescents, with a focus on lead. These investigations were conducted in the ELEMENT cohort, a longitudinal birth cohort that has been studied for over 25 years. Toxicant exposures were measured in blood and urine prenatally and in early childhood and adolescence (time, sample size, and collection type varies depending on the toxicant). Sleep was measured via wrist actigraphy when participants were in the peri-pubertal and early adulthood age range. Overall, findings indicate relationships between higher toxicant exposure with worse sleep parameters (i.e., shorter sleep duration, later sleep timing, higher fragmentation), although findings vary by toxicant and in some cases by sex.

EHS Core Center Affiliation: University of Michigan, M-LEEAD Center

Hae-Ryung Park, Ph.D., University of Rochester Medical Center

Title: Mechanisms Underlying the Effect of Environmental Exposures on Neurodevelopment (3MB)

Abstract: Disruption of neurodevelopment life due to environmental exposures can have lifelong impacts. The unique susceptibility of early brain development may be explained, in part, by the environmental impact on neural stem cells. However, the molecular mechanisms by which environmental factors impact neural stem cell functions remain poorly understood. To fill these knowledge gaps, I propose a highly integrative study combining the state of art methods, molecular mechanistic studies, human genetic epidemiology in children. We recently performed a genome-wide CRISPR screen to identify novel suppressors of arsenic (As) -induced endoplasmic reticulum (ER) stress and cell death. Among top hits from the screen, we showed that miR-124 downregulated the IRE1 branch of the ER stress pathway by directly targeting the IRE1 gene. We further showed that miR-124 protects against As-toxicity in neural stem cells and miR-124 genetic polymorphism is associated with neurodevelopmental outcomes in children. Our study implicates As-induced ER stress as a crucial mechanism for the detrimental effects of As on neural cell function and neurodevelopment and identifies miR-124 as a potential preventative and therapeutic target against detrimental effects of As exposure in children. Future studies will directly address the important mechanistic question about the critical susceptibility of early brain development to environmental exposure. I will also explore the unique yet less studied role of the placenta in regulating neural stem cell functions and environmental exposure-induced neurotoxicity. The long-term goal of this study is to contribute to the development of novel preventative and therapeutic strategies for environment related neurodevelopmental pathologies.

EHS Core Center Affiliation: University of Rochester, EHSC Center