Abstract

Among the mechanisms underlying Parkinson’s disease, many pathogenic mechanisms are suggested to be effective such as oxidative stress, mitochondrial dysfunction, disruption of the ubiquitin-proteasome system, and neuroinflammation. Calcium is very important for neuronal and glial cells, neurodegenerative disease mechanisms are closely related to disturbed calcium homeostasis. Recent studies strongly support the role of inflammation in nigrostriatal degeneration in PD. In recent years, Rifampicin, a macrocyclic antibiotic has been shown to have a protective effect on neurons. This study aims to evaluate the effects of rifampicin in the experimental PD model induced by rotenone in zebrafish focusing on the relationship between calcium-dependent mitochondrial dysfunction and inflammation. Adult zebrafish were exposed to rotenone and rifampicin for 3 weeks. Locomotor activity was determined as the total distance that the zebrafish traveled for 5 min. Neuroinflammation and PD-related gene expressions were determined by RT-PCR. Mitochondrial calcium levels were determined using inductively coupled plasma-optical emission spectrometry (ICP-OES). Gamma synuclein, Park 7, Sigma-1 receptor expressions were determined by Western Blot. Our results show that rifampicin may be effective in reducing neuroinflammation, which may be an effective strategy to reduce mitochondrial dysfunction due to impaired calcium homeostasis in PD.

摘要

在帕金森病的潜在机制中，许多致病机制被认为是有效的，例如氧化应激、线粒体功能障碍、泛素-蛋白酶体系统的破坏和神经炎症。钙对神经元和神经胶质细胞非常重要，神经退行性疾病的机制与钙稳态紊乱密切相关。最近的研究强烈支持炎症在 PD 黑质纹状体变性中的作用。近年来，大环抗生素利福平已被证明对神经元具有保护作用。本研究旨在评估利福平在斑马鱼鱼藤酮诱导的实验性 PD 模型中的作用，重点关注钙依赖性线粒体功能障碍与炎症之间的关系。成年斑马鱼暴露于鱼藤酮和利福平 3 周。运动活动被确定为斑马鱼行进 5 分钟的总距离。通过 RT-PCR 确定神经炎症和 PD 相关基因的表达。使用电感耦合等离子体发射光谱法 (ICP-OES) 测定线粒体钙水平。Gamma synuclein、Park 7、Sigma-1 受体表达通过蛋白质印迹法测定。我们的研究结果表明，利福平可能有效减少神经炎症，这可能是减少 PD 中钙稳态受损导致的线粒体功能障碍的有效策略。使用电感耦合等离子体发射光谱法 (ICP-OES) 测定线粒体钙水平。Gamma synuclein、Park 7、Sigma-1 受体表达通过蛋白质印迹法测定。我们的研究结果表明，利福平可能有效减少神经炎症，这可能是减少 PD 中钙稳态受损导致的线粒体功能障碍的有效策略。使用电感耦合等离子体发射光谱法 (ICP-OES) 测定线粒体钙水平。Gamma synuclein、Park 7、Sigma-1 受体表达通过蛋白质印迹法测定。我们的研究结果表明，利福平可能有效减少神经炎症，这可能是减少 PD 中钙稳态受损导致的线粒体功能障碍的有效策略。