The Effects of Acute and Repeated Exposure/s to the Organophosphate Pesticide Chlorpyrifos at Subthreshold Doses on Brain Structural Integrity

Abstract

Organophosphates are a class of chemicals that are used in pesticides, herbicides, and also as nerve agents. Organophosphate pesticides are ubiquitous among agricultural fields and the prolonged effects of organophosphates are not well understood. It is believed that exposure to Organophosphates can cause neurological deficits and impaired neurobehavioral function. We hypothesize that the organophosphate pesticide chlorpyrifos (CPF) is associated with mechanisms that directly and/or indirectly disrupt axonal transport in brain regions integral for learning and memory. To assay this claim, rats were treated acutely with CPF at a subtoxic dose (18 mg/kg) or with repeated exposures for 14 consecutive days at subtoxic doses (3.0, 10.0 or 18 mg/kg). Whole brain was collected 6 or 24 hours after acute exposure or directly following 14 days of repeated exposure or a 30-day drug-free washout period. For my project, I focused on the prefrontal cortex, a brain region important for executive function. Prefrontal cortex was processed using a subcellular fractionation protocol and extracts were assessed by immunoblotting methods to measure the expression of a-tubulin, a microtubule protein critical for axonal transport. Our results will help us gain insight into a potential mechanism by which CPF affects axonal transport.