School of Medicine, Medical Research Institute, Neuroscience Research Group, University of Antioquia, SIU, Medellin, Colombia.
Neurochem Res. 2011 Jun;36(6):1073-86. doi: 10.1007/s11064-011-0451-0. Epub 2011 Mar 26.
Previous studies have shown that polyphenols might be potent neuroprotective agents in Drosophila melanogaster, a valid model for PD, acutely treated with oxidative stress-stimulants. This study report for the first time that polyphenols exposure prolong life span (P < 0.05 by log-rang test) and restore locomotor activity (i.e., climbing capability, P < 0.05 by χ(2) test) of Drosophila melanogaster chronically exposed to paraquat compared to flies treated with paraquat alone in 1% glucose. We found that (10%) glucose partially prolongs life span and climbing in Drosophila exposed to iron, PQ or in combination, suggesting that both stimuli enhance a movement disorder in a concentration-dependent and temporal-related fashion. Moreover, chronic exposure of (1 mM) PQ/(0.5 mM) iron synergistically affect both survival and locomotor function independently of the temporal order of the exposure to the toxicants, but the survival is modulated in a concentration and temporal fashion by glucose. This investigation is the first to report that Ddc-GAL4 transgenic flies chronically fed with polyphenols increase life span (P < 0.05 by log-rang test) and enhance movement abilities (P < 0.05 by χ(2) test) compared to untreated Ddc-GAL4 or treated with paraquat in 1% glucose. Our present findings support the notion that Drosophila melanogaster might be a suitable model to study genetic, environmental and nutritional factors as causal and/or modulators in the development of PD. Most importantly, according to our model, we have demonstrated for the first time chronic polyphenols exposure as potential therapeutic compounds in the treatment of PD. These findings altogether open new avenues for the screening, testing and development of novel antioxidant drugs against oxidative stress stimuli.
先前的研究表明,多酚类化合物可能是一种有效的帕金森病(PD)模型果蝇中具有强大神经保护作用的物质,可对其进行急性氧化应激刺激处理。本研究首次报道,与单独用百草枯处理的果蝇相比,慢性接触百草枯的果蝇寿命(对数秩检验,P < 0.05)和运动活性(即攀爬能力,卡方检验,P < 0.05)得以延长,而这些果蝇在 1%葡萄糖中接触了多酚类化合物。我们发现,(10%)葡萄糖可部分延长接触铁、百草枯或两者组合的果蝇的寿命和攀爬能力,表明这两种刺激物均以浓度依赖性和时间相关的方式增强运动障碍。此外,慢性接触(1 mM)百草枯/(0.5 mM)铁可协同影响生存和运动功能,而与接触毒物的时间顺序无关,但葡萄糖可调节生存时间和方式。本研究首次报道,与未处理的 Ddc-GAL4 或在 1%葡萄糖中用百草枯处理的 Ddc-GAL4 相比,慢性喂食多酚类化合物的 Ddc-GAL4 转基因果蝇可延长寿命(对数秩检验,P < 0.05)并增强运动能力(卡方检验,P < 0.05)。我们目前的研究结果支持以下观点,即黑腹果蝇可能是研究遗传、环境和营养因素作为 PD 发病的因果和/或调节因素的合适模型。最重要的是,根据我们的模型,我们首次证明慢性多酚类化合物暴露可能是治疗 PD 的潜在治疗化合物。这些发现为筛选、测试和开发针对氧化应激刺激的新型抗氧化药物开辟了新的途径。