Bio-Behavioral Analysis of a Dual-Exposure Pesticide Model and its Implications in a Silent Vulnerability to Parkinson's Disease

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor disturbances and a loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). High rates of idiopathic PD have been linked to environmental factors, including pesticide exposure. Research has suggested that pre-natal treatment with maneb, a fungicide, may imbue a silent vulnerability to PD that is only unmasked in adulthood during subsequent exposure to the herbicide paraquat. The purpose of this study was to confirm the developmental results found in the dual-exposure pesticide model using different behavioral and neurochemical measures. Pregnant C57BL/6J mice were treated with a 1mg/kg dose of maneb or an equivalent dose of saline on gestational days 10-17. The offspring were then injected with a 5mg/kg dose of paraquat or saline on postnatal days 48-55. On postnatal day 60, mice were given three behavioral tasks: open field, pole climb, and swim test. Nuclear Magnetic Resonance (NMR) spectroscopy was performed to quantify neurometabolite concentrations. We hypothesize that there will be significant changes in locomotor behavior between the maneb- paraquat group and the other two experimental groups and no significant differences evident between the saline-saline control group and the maneb-saline group. Finally, we expect NMR analysis to reveal differences in neurometabolite concentrations suggesting that the nigrostriatal dopaminergic neurons have been comprimised. If our hypotheses are correct, it would provide more evidence to support the dual-exposure pesticide model and imply that prenatal exposure to maneb potentiates the effects of paraquat and mimics a silent vulnerability pathway for Parkinson’s disease within the Fetal Basis of Adult Disease (FeBAD) model.