Abstract：
Parkinson\'s disease (PD) is a prevalent neurodegenerative disorder, characterized by motor and psychological dysfunction. Palliative treatment and dopamine replenishment therapy are the only available therapeutic options. Calcium channel blockers (CCBs) have been reported to protect against several neurodegenerative disorders. The current study was designed to evaluate the neuroprotective impact of Felodipine (10 mg/kg, orally) as a CCB on motor and biochemical dysfunction associated with experimentally induced PD using rotenone (2.5 mg/kg, IP) and to investigate the underlying mechanisms. Rotenone induced deleterious neuromotor outcomes, typical of those associated with PD. The striatum revealed increased oxidative burden and NO levels with decreased antioxidant capacity. Nrf2 content significantly decreased with the accumulation of α-synuclein and tau proteins in both the substantia nigra and striatum. These observations significantly improved with felodipine treatment. Of note, felodipine increased dopamine levels in the substantia nigra and striatum as confirmed by the suppression of inflammation and the significant reduction in striatal NF-κB and TNF-α contents. Moreover, felodipine enhanced mitophagy, as confirmed by a significant increase in mitochondrial Parkin and suppression of LC3a/b and SQSTM1/p62. In conclusion, felodipine restored dopamine synthesis, attenuated oxidative stress, inflammation, and mitochondrial dysfunction, and improved the mitophagy process resulting in improved PD-associated motor impairment.
摘要：
帕金森病(PD)是一种普遍的神经退行性疾病,以运动和心理功能障碍为特征。姑息治疗和多巴胺补充治疗是唯一可用的治疗选择。钙通道阻滞剂（CCB）已被报道可以预防几种神经退行性疾病。本研究旨在评估非洛地平（10mg/kg，口服）作为CCB对与使用鱼藤酮（2.5mg/kg，IP)并调查潜在机制。鱼藤酮诱导有害的神经运动结果，与PD有关的典型。纹状体显示氧化负荷和NO水平增加，抗氧化能力降低。随着黑质和纹状体中α-突触核蛋白和tau蛋白的积累，Nrf2含量显着降低。这些观察结果在非洛地平治疗下显著改善。值得注意的是，非洛地平增加了黑质和纹状体中的多巴胺水平，这通过抑制炎症和纹状体NF-κB和TNF-α含量的显着降低得到了证实。此外，非洛地平增强线粒体自噬，线粒体Parkin的显着增加和LC3a/b和SQSTM1/p62的抑制证实了这一点。总之,非洛地平恢复多巴胺合成，减弱的氧化应激，炎症,和线粒体功能障碍，并改善了线粒体自噬过程，从而改善了PD相关的运动障碍。
