The primary etiology of Parkinson’s disease (PD) remains unclear, but likely reflects a combination of genetic and environmental factors. Exposure to some pesticides, including ziram (zinc dimethyldithiocarbamate), is a relevant risk factor for PD. Like some other environmental neurotoxicants, we hypothesized that ziram can enter the central nervous system from the nasal mucosa via the olfactory nerves. To address this issue, we evaluated the effects of 1, 2 or 4 days of intranasal (i.n., 1 mg/nostril/day) infusions of sodium dimethyldithiocarbamate (NaDMDC), a dimethyldithiocarbamate more soluble than ziram, on locomotor activity in the open field, neurological severity score and rotarod performance. We also addressed the effects of four daily i.n. NaDMDC infusions on olfactory bulb (OB) and striatal measures of cell death, reactive oxygen species (ROS), tyrosine hydroxylase, and the levels of dopamine, noradrenaline, serotonin, and their metabolites. A single i.n. administration of NaDMDC did not significantly alter the behavioral measures. Two consecutive days of i.n. NaDMDC administrations led to a transient neurological deficit that spontaneously resolved within a week. However, the i.n. infusions of NaDMDC for 4 consecutive days induced motor and neurological deficits for up to 7 days after the last NaDMDC administration and increased striatal TH immunocontent and dopamine degradation within a day of the last infusion. Pharmacological treatment with the anti-parkinsonian drugs l-DOPA and apomorphine improved the NaDMDC-induced locomotor deficits. NaDMDC increased serotonin levels and noradrenaline metabolism in the OB 24 h after the last NaDMDC infusion, ROS levels in the OB 2 h after the last infusion, and striatum 2 and 24 h after the last infusion. These results demonstrate, for the first time, that i.n. NaDMDC administration induces neurobehavioral and neurochemical impairments in mice. This accords with evidence that dimethyldithio-carbamate exposure increases the risk of PD and highlights the possibility that olfactory system could be a major route for NaDMDC entry to central nervous system.

帕金森氏病（PD）的主要病因尚不清楚，但可能反映了遗传因素和环境因素的结合。暴露于某些农药，包括齐拉姆（二甲基二硫代氨基甲酸锌）是PD的相关危险因素。像其他一些环境神经毒剂一样，我们假设齐拉姆可以通过鼻粘膜从中枢神经系统进入中枢神经系统。嗅觉神经。为了解决这个问题，我们评估了在野外通过鼻内输注二甲基二硫代氨基甲酸钠（NaDMDC）（其比ziram更易溶解）的1、2或4天（1 mg /鼻孔/天）对运动活动的影响，神经系统严重程度评分和轮转表现。我们还探讨了NaDMDC每天四次输注对嗅球（OB）和纹状体细胞死亡，活性氧（ROS），酪氨酸羟化酶以及多巴胺，去甲肾上腺素，5-羟色胺及其代谢物水平的影响。NaDMDC的单次使用并没有显着改变行为指标。在NaDMDC中连续两天服用会导致短暂的神经功能缺损，并在一周内自发消失。但是，在 连续4天输注NaDMDC会在最后一次输注NaDMDC后长达7天之内引起运动和神经功能障碍，并在最后输注的一天之内增加纹状体TH免疫含量和多巴胺降解。抗帕金森氏症药物的药理治疗1- DOPA和阿扑吗啡改善了NaDMDC引起的运动功能障碍。最后一次输注NaDMDC后24 h，NaDMDC增加OB中的血清素水平和去甲肾上腺素代谢，最后一次输注后2 h，以及最后一次输注后纹状体2和24 h，OB中的ROS水平升高。这些结果首次证明，在NaDMDC中给药可诱发小鼠神经行为和神经化学损伤。这符合以下证据：二甲基二硫代氨基甲酸酯暴露会增加发生PD的风险，并突显了嗅觉系统可能是NaDMDC进入中枢神经系统的主要途径的可能性。