The effects of developmental chlorpyrifos exposure on the proteome of the adolescent rat hippocampus

Chlorpyrifos is a widely used organophosphate insecticide, functioning through the inhibition of acetylcholinesterase. Recent studies report negative long-lasting biochemical and behavioral effects at levels without acetylcholinesterase inhibition. Our lab studies have identified the endocannabinoid system as a target for OP low-dose neurotoxicity. This thesis identifies the proteins and their associated neurotransmitter systems in the hippocampus that have been affected by low dose developmental exposure to the OP insecticide CPF. Male rat pups were treated from postnatal day 10 (PND) - PND16 with either corn oil (vehicle), 0.75 mg/kg of CPF, or 0.02 mg/kg of PF-04457845, a specific fatty acid amide hydrolase (FAAH) inhibitor. On PND38, rats were sacrificed for hippocampal extraction, and shotgun proteomics was used for protein expression. DAVID and Ingenuity Pathway Analysis software detected differentially expressed proteins such as Neuroligin-2 and Synaptotagmin 2, and disrupted signaling pathways such as ephrin B signaling, synaptogenesis signaling, and glutamate receptor signaling. Taken together, our data suggests that CPF reduces glutaminergic signaling pathways, greatly reducing long-term potentiation, prohibiting proper synapse formation, and therefore disrupting the proper functioning of the hippocampus