Evaluation of developmental and long-term effects of chlorpyrifos in PC-12 cells
Authors:Brianna Ahn, Juan Garcia, Sarah Meuwissen
Mentor:Erica Fradinger, Assistant Professor of Biology, Whittier College
Chlorpyrifos is a widely used organophosphate pesticide that inhibits the enzyme acetylcholinesterase preventing the degradation of the neurotransmitter acetylcholine. The resulting hyperstimulation of cholinergic neurons affects their development, function, and survival. In this study we used rat pheochromocytoma (PC-12) cells to examine the effects of chlorpyrifos on developing cholinergic neurons. Nerve growth factor stimulates the differentiation of PC-12 cells into neurons with a cholinergic phenotype. Dose-dependent cell death was observed for PC-12 cells exposed to chlorpyrifos during differentiation. Results also indicate that PC-12 cells were more sensitive to chlorpyrifos during mid-late stages of differentiation than earlier stages at a time when mature synapses are forming. Surprisingly, long-term exposure to chlorpyrifos at sub-lethal concentrations beginning at differentiation decreased their susceptibility to hydrogen peroxide-induced oxidative stress. These results indicate that cholinergic hyperstimulation adversely effects neurons during differentiation, but may be protective against oxidative stress in mature neurons.