Developmental exposure to organophosphorus pesticide to evaluate airway hyperreactivity Epidemiological studies have linked organophosphorus pesticide (OP) exposure to increased risk of asthma in children and adults, yet preclinical evidence supporting this causal link is limited. Dr. Grodzki’s previous work has shown that the OP chlorpyrifos causes airway hyperreactivity (AHR) at low doses that do not inhibit acetylcholinesterase. However, current understanding of the mechanisms involved in OP-induced AHR is incomplete and the question of whether developmental OP exposure could lead to asthmatic symptoms has not been addressed in preclinical models. Dr. Grodzki is investigating the effects of developmental chlorpyrifos exposures on AHR using physiological measurements of lung function and markers of neurogenic inflammation in animal models.
Behavioral and neuroimaging phenotypes following early life pesticide exposure Worldwide, organophosphate pesticides are the most commonly used class of pesticides. Epidemiological studies have linked their use to autism, attention deficit hyperactivity disorder, developmental delay, and other neurodevelopmental disorders. Currently, the impacts of early-life exposure to low doses that are representative of what people and, in particular, pregnant women and children may experience, have not been well-studied. Dr. Silverman’s project is measuring the effects of exposure to chlorpyrifos, a widely used organophosphate, during early life on behavioral endpoints and underlying brain anomalies in a rodent model.
Maternal Metabolome, PON1 Status, Organophosphate Exposure and Childhood Autism With the rapid rise in autism spectrum disorder (ASD) diagnoses over the last three decades, identification of the causes and mechanisms of this condition is urgently needed. Building on recent findings that children prenatally exposed to pesticides have an increased risk of an ASD diagnosis, serum from children was previously analyzed. A distinct metabolic pattern was found in children with ASD who were exposed to pesticides in utero that revealed associations with insulin regulation. Given the correlation between insulin resistance and decreased activity of paraoxonase 1 (or PON1, an enzyme involved in detoxification), we hypothesize that exposure to pesticides during pregnancy coupled with reduced maternal PON1 activity is associated with the metabolic health of the mother and the neurological outcome and metabolic health of her child. Most of the evidence about environmental factors in autism provides sparse information about the biologic mechanisms of neurodevelopment. This project seeks to generate preliminary data on perturbations in basic biochemical pathways and reduced PON1 status as a consequence of pesticide exposure, and its association with autism in children.