Dalui Shauryabrota, Bhattacharyya Arindam
Indian J Biochem Biophys. 2014 Dec;51(6):567-73.
There are several reports on herbicide paraquat (PQ)-induced Parkinsonian-like pathology in different animal models, including Drosophila melanogaster. Also, the role of some inflammatory factors, such as nitric oxide is reported in PQ-induced neuroinflammation of Drosophila. Although invertebrate model is valuable to study the conserved inflammatory pathway at the time of neurodegeneration, but neuroinflammation during PQ-mediated neurodegeneration has not been studied explicitly in Drosophila. In this study, the inflammatory response was examined in Drosophila model during PQ-induced neurodegeneration. We found that after exposure to PQ, survivability and locomotion ability were affected in both sexes of Drosophila. Behavioural symptoms indicated similar physiological features of Parkinson's disease (PD) in different animal models, as well as in humans. Our study revealed alteration in proinflamatory factor, TNF-α and Eiger (the Drosophila homologue in TNF superfamily) was changed in PQ-treated Drosophila both at protein and mRNA level during neurodegeneration. To ensure the occurrence of neurodegeneration, tyrosine hydroxylase (TH) positive neuronal cell loss was considered as a hallmark of PD in the fly brain. Thus, our result revealed the conserved inflammatory events in terms of expression of TNF-α and Eiger present during a sublethal dose of PQ-administered neurodegeneration in male and female Drosophila with significant variation in proinflammatory factor level among both the sexes.
有几篇关于除草剂百草枯(PQ)在包括黑腹果蝇在内的不同动物模型中诱导帕金森样病理的报道。此外,也有报道称一些炎症因子,如一氧化氮在PQ诱导的果蝇神经炎症中发挥作用。尽管无脊椎动物模型对于研究神经退行性变时保守的炎症途径很有价值,但PQ介导的神经退行性变过程中的神经炎症在果蝇中尚未得到明确研究。在本研究中,我们在PQ诱导的神经退行性变过程中检测了果蝇模型中的炎症反应。我们发现,暴露于PQ后,果蝇雌雄两性的生存能力和运动能力均受到影响。行为症状表明,在不同动物模型以及人类中,帕金森病(PD)具有相似的生理特征。我们的研究表明,在神经退行性变过程中,经PQ处理的果蝇在蛋白质和mRNA水平上,促炎因子肿瘤坏死因子-α(TNF-α)和埃iger(TNF超家族中的果蝇同源物)均发生了变化。为确保神经退行性变的发生,酪氨酸羟化酶(TH)阳性神经元细胞的丢失被视为果蝇大脑中PD的一个标志。因此,我们的结果揭示了在亚致死剂量的PQ诱导的神经退行性变过程中,雄性和雌性果蝇中TNF-α和埃iger表达方面保守的炎症事件,且两性之间促炎因子水平存在显著差异。