Developmental Pyrethroid Exposure and Parkinsons Disease

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DESCRIPTION (provided by applicant): Both genetic and environmental factors play key roles in the pathological manifestation of Parkinson's Disease (PD). Epidemiological studies have identified pesticide exposure as a specific risk factor for PD. Our lab and others have shown that the commonly used pesticide, deltamethrin, alters the expression and function of the dopamine transporter in adult mice. The dopamine transporter is a key regulator of dopaminergic neurotransmission and a gateway for dopaminergic toxins, such as MPTP. Thus, alteration of its function or expression may increase the susceptibility of dopamine neurons to damage by neurotoxins such as MPTP and the neurotransmitter dopamine by increasing their uptake into dopamine neurons. We now provide evidence that gestational and lactational exposure to deltamethrin at levels lower than used in the adult studies leads to long-term up-regulation of the dopamine transporter. Therefore, the purpose of this study is to examine the effects of deltamethrin on the development of the nigrostriatal dopamine system and to determine if such exposures increase the susceptibility of these animals to the parkinsonism-inducing neurotoxin MPTP.