Exposure to fungicide ziram (zinc dimethyldithiocarbamate) has been associated with increased incidence of Parkinson’s disease (PD). We recently demonstrated that the intranasal (i.n.) administration of sodium dimethyldithiocarbamate (NaDMDC, a more soluble salt than ziram) induces PD-like behavioral and neurochemical alterations in mice. We now investigated the putative neuroprotective effects of melatonin on behavioral dificits and neurochemical alterations induced by i.n. NaDMDC. Melatonin treatment (3, 10 or 30 mg/kg, i.p.) was given 1 h before NaDMDC administration (1 mg/nostril) during 4 consecutive days and we evaluated early (up to 7 days) and late (up to 35 days) NaDMDC-induced behavioral and neurochemical alterations. Melatonin treatment protected against early motor and general neurological impairments observed in the open field and neurological score of severity, respectively, and late deficits in rotarod test. Melatonin prevented the NaDMDC-induced alterations in the striatal tyrosine hydroxylase immunocontent. Melatonin also protected against increased levels of oxidative stress markers (4-hydroxynonenal and 3-nitrotyrosine) in the striatum, as well as the NaDMDC-induced increase of 4-hydroxynonenal and TNF, markers of oxidative stress and inflammation, respectively, in the olfactory bulb. These results further detail the mechanisms underlying NaDMDC toxicity and demonstrate the neuroprotective effects of melatonin against the neuronal damage induced by NaDMDC.

暴露于杀菌剂齐拉姆（二甲基二硫代氨基甲酸锌）与帕金森氏病（PD）的发病率增加有关。我们最近证明了鼻内二甲基二硫代氨基甲酸钠（NaDMDC，比齐拉姆更易溶的盐）的给药在小鼠中诱导了PD样的行为和神经化学改变。我们现在调查了褪黑素对NaDMDC引起的行为差异和神经化学改变的假定的神经保护作用。连续4天在给予NaDMDC（1 mg /鼻孔）前1小时给予褪黑激素治疗（3、10或30 mg / kg，ip），我们评估了NaDMDC的早期（长达7天）和晚期（长达35天）引起的行为和神经化学改变。褪黑素治疗可防止在旷野和严重程度的神经系统评分中分别观察到早期运动和一般神经功能障碍，以及轮状试验中晚期缺陷。褪黑素阻止了NaDMDC诱导的纹状体酪氨酸羟化酶免疫含量的改变。褪黑素还可以防止纹状体中氧化应激标志物（4-羟基壬烯醛和3-硝基酪氨酸）水平升高，以及NaDMDC诱导的嗅觉中氧化应激和炎症标志物4-羟基壬烯醛和TNF的升高。灯泡。这些结果进一步详述了NaDMDC毒性的潜在机制，并证明了褪黑激素对NaDMDC诱导的神经元损伤的神经保护作用。褪黑素阻止了NaDMDC诱导的纹状体酪氨酸羟化酶免疫含量的改变。褪黑素还可以防止纹状体中氧化应激标志物（4-羟基壬烯醛和3-硝基酪氨酸）水平升高，以及NaDMDC诱导的嗅觉中氧化应激和炎症标志物4-羟基壬烯醛和TNF的升高。灯泡。这些结果进一步详述了NaDMDC毒性的潜在机制，并证明了褪黑激素对NaDMDC诱导的神经元损伤的神经保护作用。褪黑素阻止了NaDMDC诱导的纹状体酪氨酸羟化酶免疫含量的改变。褪黑素还可以防止纹状体中氧化应激标志物（4-羟基壬烯醛和3-硝基酪氨酸）水平升高，以及NaDMDC诱导的嗅觉中氧化应激和炎症标志物4-羟基壬烯醛和TNF的升高。灯泡。这些结果进一步详述了NaDMDC毒性的潜在机制，并证明了褪黑激素对NaDMDC诱导的神经元损伤的神经保护作用。嗅球中氧化应激和炎症的标志物 这些结果进一步详述了NaDMDC毒性的潜在机制，并证明了褪黑激素对NaDMDC诱导的神经元损伤的神经保护作用。嗅球中的氧化应激和炎症标志物 这些结果进一步详述了NaDMDC毒性的潜在机制，并证明了褪黑激素对NaDMDC诱导的神经元损伤的神经保护作用。