Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu, 600 025, India.
Environ Sci Pollut Res Int. 2019 May;26(14):14461-14472. doi: 10.1007/s11356-019-04740-y. Epub 2019 Mar 13.
Rotenone (ROT) was shown to affect cerebral ganglions (CGs) of Lumbricus terrestris as a pioneering observation in our earlier investigation. Though ROT is a well-known neurotoxin causing neurodegeneration (ND), the precipitation of movement dysfunction remains largely unknown. We have designed the current study to analyze motor abnormalities in worms by exposing them to different concentrations (0.0-0.4 ppm) of ROT for 7 days. GABA, cholinergic receptor, serotonin transporter (SERT), acetylcholine esterase (AchE), and dopamine-β-hydroxylase that are well known for their involvement in neuromuscular junctions were investigated by qRT-PCR. Further, neuronal mitochondrial genes (cytochrome C oxidase-2, NADH deydrogenase-1, cytochrome-b) and actin-1 that are essential for regeneration and calreticulin (phagocytosis) were investigated. The levels of neurotransmitters, lipids, ATPase, neuronal behavior analyses, and fluorescence analysis (lipid droplets) were performed in CGs which showed significant variations at 0.3 ppm. Ultrastructural changes in lipid droplet and neuromelatonin were prominent in 0.3 ppm. Dose-dependent effect of ROT on behavior alteration and expression of m-RNAs studied suggested that at 0.3 ppm, it could deteriorate motor and cognitive functions. We predict that perhaps, by virtue of its effect on cerebral ganglionic genes and their neurotransmitting potential, ROT may cause morbidities that resemble features characteristic of hemiparkinsonic degeneration.
鱼藤酮 (ROT) 被证明会影响赤子爱胜蚓的脑神经节 (CGs),这是我们早期研究中的一个开创性观察结果。尽管 ROT 是一种众所周知的神经毒素,会导致神经退行性变 (ND),但运动功能障碍的加剧在很大程度上仍不清楚。我们设计了当前的研究,通过将蠕虫暴露于不同浓度 (0.0-0.4 ppm) 的 ROT 中 7 天来分析蠕虫的运动异常。GABA、胆碱能受体、5-羟色胺转运体 (SERT)、乙酰胆碱酯酶 (AchE) 和多巴胺-β-羟化酶,这些都是众所周知的参与神经肌肉接头的物质,通过 qRT-PCR 进行了研究。此外,还研究了神经元线粒体基因 (细胞色素 C 氧化酶-2、NADH 脱氢酶-1、细胞色素-b) 和肌动蛋白-1,它们对于再生和钙网蛋白 (吞噬作用) 是必不可少的。神经递质、脂质、ATP 酶、神经元行为分析和 CGs 中的荧光分析 (脂质滴) 的水平在 0.3 ppm 时显示出显著变化。在 0.3 ppm 时,脂质滴和神经褪黑素的超微结构变化非常明显。ROT 对行为改变和 m-RNA 表达的剂量依赖性影响研究表明,在 0.3 ppm 时,它可能会恶化运动和认知功能。我们预测,也许由于其对大脑神经节基因及其神经递质潜力的影响,ROT 可能会导致类似于偏侧 parkinson 变性特征的病态。