Developmental Pyrethroid Exposure and Parkinsons Disease

描述(由申请人提供)： 遗传因素和环境因素在帕金森病(PD)的病理表现中起着关键作用。流行病学研究已确定农药暴露是帕金森病的具体危险因素。我们的实验室和其他实验室已经证明，常用的杀虫剂溴氰菊酯可以改变成年小鼠的多巴胺转运体的表达和功能。多巴胺转运体是多巴胺能神经传递的关键调节因子，也是多巴胺能毒素如MPTP的通道。因此，其功能或表达的改变可能会增加多巴胺神经元对MPTP等神经毒素和神经递质多巴胺的易感性，从而增加它们对多巴胺神经元的摄取。我们现在提供的证据表明，孕期和哺乳期接触溴氰菊酯的水平低于成人研究中使用的水平，会导致多巴胺转运体的长期上调。因此，本研究的目的是研究溴氰菊酯对黑质纹状体多巴胺系统发育的影响，并确定这种暴露是否会增加这些动物对帕金森症诱导的神经毒素MPTP的易感性。

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.