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黑腹果蝇对百草枯诱导的帕金森病的年龄相关耐受性

Age-related tolerance to paraquat-induced parkinsonism in Drosophila melanogaster.

作者信息

Neves Paula Fernanda Ribas, Milanesi Bruna Bueno, Paz Lisiê Valéria, de Miranda Monteiro Valentina Aguiar Cardozo, Neves Laura Tartari, da Veiga Louise Cordoni, da Silva Rafaela Barboza, Sulzbach Juliana Henz, Knijkik Gabriela Padilla, de Revoredo Ribeiro Eduarda Correa, de Souza Silva Ellen Larissa, Vieira Moema Queiroz, Bagatini Pamela Brambilla, Wieck Andrea, Mestriner Régis Gemerasca, Xavier Léder Leal

机构信息

Laboratório de Biologia Celular e Tecidual, Escola de Ciências, da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.

Laboratório de Biologia Celular e Tecidual, Escola de Ciências, da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.

出版信息

Toxicol Lett. 2022 May 15;361:43-53. doi: 10.1016/j.toxlet.2022.03.010. Epub 2022 Mar 31.

DOI:10.1016/j.toxlet.2022.03.010
PMID:35367327
Abstract

Paraquat (PQ) is a widely used herbicide that can cross the dopaminergic neuronal membrane, accumulate in mitochondria and damage complex I of the electron transport chain, leading to neuronal death. In Drosophila melanogaster, PQ exposure leads to the development of parkinsonism and is a classical model for studying Parkinson's Disease (PD). Muscle mitochondrial dysfunction, affecting survival and locomotion, is described in familial PD in D. melanogaster mutants. However, no study has shown the effects of PQ-induced parkinsonism in D. melanogaster regarding muscle ultrastructure and locomotor behavior at different ages. Thus, we evaluated survival, locomotion, and morphological parameters of mitochondria and myofibrils using transmission electron microscopy in 2 and 15-day-old D. melanogaster, treated with different PQ doses: control, 10, 50, 100, 150, and 200 mM. PQ100mM presented 100% lethality in 15-day-old D. melanogaster, while in 2-day-old animals PQ150mM produced 20% lethality. Bradykinesia was only observed in 15-day-old D. melanogaster treated with PQ10 mM and PQ50 mM. However, these results are unlikely to be associated with changes to morphology. Taken together, our data indicate pathophysiological differences between PQ-induced parkinsonism and familial parkinsonism in D. melanogaster (resultant from gene mutations), demonstrating for the first time a differential susceptibility to PQ in two developmental stages.

摘要

百草枯(PQ)是一种广泛使用的除草剂,它能够穿过多巴胺能神经元膜,在线粒体中蓄积并损害电子传递链复合体I,从而导致神经元死亡。在黑腹果蝇中,接触PQ会导致帕金森综合征的发生,是研究帕金森病(PD)的经典模型。在黑腹果蝇突变体的家族性PD中,描述了影响生存和运动的肌肉线粒体功能障碍。然而,尚无研究表明PQ诱导的黑腹果蝇帕金森综合征在不同年龄阶段对肌肉超微结构和运动行为的影响。因此,我们使用透射电子显微镜评估了用不同PQ剂量(对照、10、50、100、150和200 mM)处理的2日龄和15日龄黑腹果蝇的生存、运动以及线粒体和肌原纤维的形态学参数。PQ100 mM在15日龄黑腹果蝇中呈现100%致死率,而在2日龄动物中,PQ150 mM产生20%的致死率。运动迟缓仅在接受PQ10 mM和PQ50 mM处理的15日龄黑腹果蝇中观察到。然而,这些结果不太可能与形态学变化相关。综上所述,我们的数据表明PQ诱导的黑腹果蝇帕金森综合征与家族性帕金森综合征(由基因突变导致)之间存在病理生理差异,首次证明了在两个发育阶段对PQ的易感性不同。

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引用本文的文献

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In vivo and in silico models of Drosophila for Parkinson's disease.用于帕金森病研究的果蝇体内和计算机模拟模型。
FEBS J. 2025 Jun 1. doi: 10.1111/febs.70140.
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The neurotoxicity of Paraquat and its degradation products on drosophila melanogaster.百草枯及其降解产物对黑腹果蝇的神经毒性。
Sci Rep. 2025 May 12;15(1):16447. doi: 10.1038/s41598-025-86413-0.
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Towards improved screening of toxins for Parkinson's risk.致力于改进帕金森病风险毒素筛查。
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