Rayatpour Atefeh, Foolad Forough, Javan Mohammad
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Institute for Brain and Cognition, Tarbiat Modares University, Tehran, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan;398(1):715-727. doi: 10.1007/s00210-024-03314-1. Epub 2024 Jul 24.
Remyelination refers to myelin regeneration, which reestablishes metabolic supports to axons. However, remyelination often fails in multiple sclerosis (MS), leading to chronic demyelination and axonal degeneration. Therefore, pharmacological approaches toward enhanced remyelination are highly demanded. Recently, deferiprone (DFP) was reported to exert neuroprotective effects, besides its iron-chelating ability. Since DFP exerts protective effects through various mechanisms, which share several factors with myelin formation process, we aimed to investigate the effects of DFP treatment on remyelination. Focal demyelination was induced by injection of lysolecithin, into the optic nerve of male C57BL/6J mice. The animals were treated with DFP/vehicle, starting from day 7 and continued during the myelin repair period. Histopathological, electrophysiological, and behavioral studies were used to evaluate the outcomes. Results showed that DFP treatment enhanced remyelination, decreased g-ratio and increased myelin thickness. At the mechanistic level, DFP enhanced oligodendrogenesis and ameliorated gliosis during the remyelination period. Furthermore, our results indicated that enhanced remyelination led to functional recovery as evaluated by the electrophysiological and behavioral tests. Even though the exact molecular mechanisms by which DFP-enhanced myelin repair remain to be elucidated, these results raise the possibility of using deferiprone as a therapeutic agent for remyelination therapy in MS.
髓鞘再生是指髓鞘的再生，它为轴突重新建立代谢支持。然而，在多发性硬化症（MS）中，髓鞘再生常常失败，导致慢性脱髓鞘和轴突退化。因此，迫切需要增强髓鞘再生的药理学方法。最近，据报道去铁酮（DFP）除了具有铁螯合能力外，还具有神经保护作用。由于DFP通过多种机制发挥保护作用，这些机制与髓鞘形成过程有几个共同因素，我们旨在研究DFP治疗对髓鞘再生的影响。通过向雄性C57BL/6J小鼠的视神经注射溶血卵磷脂诱导局灶性脱髓鞘。从第7天开始用DFP/载体对动物进行治疗，并在髓鞘修复期持续给药。采用组织病理学、电生理学和行为学研究来评估结果。结果表明，DFP治疗可增强髓鞘再生，降低g比值并增加髓鞘厚度。在机制层面，DFP在髓鞘再生期增强少突胶质细胞生成并改善胶质增生。此外，我们的结果表明，通过电生理学和行为学测试评估，增强的髓鞘再生导致功能恢复。尽管DFP增强髓鞘修复的确切分子机制仍有待阐明，但这些结果增加了将去铁酮用作MS髓鞘再生治疗药物的可能性。
