Mechanisms of pesticide-induced neuroinflammation and parkinsonism in aging mice

This research program focused on the molecular mechanisms that connect environmental toxicant exposures to neuroinflammation and Parkinson’s disease–like pathology, with an emphasis on aging.

This laboratory concentrates on how interactions between pesticides and the innate immune system drive progressive neurodegenerative changes, using established models of pesticide exposure and genetic and molecular tools to interrogate key inflammatory pathways. A central theme across the researchers' work is the role of the NLRP3 inflammasome and related innate immune signaling in mediating neuronal vulnerability following chronic toxicant exposure. Publications from this group documents that genetic and molecular manipulation of inflammasome-related genes alters outcomes in neurons and in vivo models exposed to pesticides, supporting the inflammasome as a mechanistic link between environmental exposures and neurodegeneration.

The lab has examined organophosphate pesticides such as chlorpyrifos and mitochondrial complex I inhibitors like rotenone as environmental triggers, demonstrating that loss or modulation of specific apoptotic or inflammasome-associated factors can influence neuronal survival and protein clearance. These findings are complemented by studies of plasma indicators of inflammasome activity in Parkinson’s disease patients and by translational efforts to identify immunological shifts early in disease using longitudinal blood-based methylation and other biomarkers.

This program is at the intersection of environmental health, immunology, and neurodegeneration, with a primary goal of defining mechanisms by which pesticide exposure produces neuroinflammation and parkinsonism-like phenotypes in aging mice. The research employs both chronic exposure paradigms and genetically modified mice to model progressive behavioral abnormalities, nigral cell loss, and inflammatory changes characteristic of Parkinsonian pathology, thereby providing a platform to test causative relationships and potential modifiers of disease progression. Supported by the National Institute for Environmental Health Sciences, these investigations are anticipated to contribute mechanistic insight that will inform biomarker development and therapeutic strategies aimed at mitigating pesticide-associated neuroinflammation and parkinsonism in aging populations.