School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences and Health Services, Isfahan, Iran.
Azarmehr Pathology Laboratory, Isfahan, Iran.
Metab Brain Dis. 2021 Oct;36(7):2101-2110. doi: 10.1007/s11011-021-00802-8. Epub 2021 Aug 3.
It has been shown that following demyelination, Oligodendrocyte Progenitor Cells (OPCs) migrate to the lesion site and begin to proliferate, and differentiate. This study aimed to investigate the effects of Hydroxychloroquine (HCQ) on the expression of OLIG-2 and PDGFR-α markers during the myelination process. C57BL/6 mice were fed cuprizone pellets for 5 weeks to induce demyelination and return to a normal diet for 1 week to stimulate remyelination. During the Phase I all of the animals except CPZ and Vehicle groups were exposed to HCQ (2.5, 10, and 100 mg/kg) via drinking water. At the end of the study, animals were euthanized, perfused and the brain samples were assessed for myelination and immunohistochemistry evaluation. What is remarkable is the high rate of Olig2 + cells in the groups treated with 10 and 100 mg/kg HCQ in the demyelination phase and its decreasing trend in the remyelination phase. However, there was no significant difference between groups during phase I and Phase II based on the percentage of olig-2+/total cells in the corpus callosum region. The number of PDGFR-α+ cells in the group treated with 10 mg/kg HCQ was significant in the first phase (p value < 0.05). Considering that the 100 mg/kg HCQ group had the highest level of PDGFR-α as well as the highest level of myelin repair in LFB staining, it could be inferred that it was the most effective dose in inducing proliferation and migration of OPCs.
已经表明,在脱髓鞘后,少突胶质前体细胞(OPC)迁移到病变部位并开始增殖和分化。本研究旨在探讨羟氯喹(HCQ)在髓鞘形成过程中对 OLIG-2 和 PDGFR-α 标志物表达的影响。C57BL/6 小鼠喂食杯状多聚体 5 周以诱导脱髓鞘,然后恢复正常饮食 1 周以刺激髓鞘再生。在第 I 阶段,除 CPZ 和 Vehicle 组外,所有动物均通过饮用水暴露于 HCQ(2.5、10 和 100mg/kg)。研究结束时,处死动物,灌注并评估大脑样本的髓鞘形成和免疫组织化学评估。值得注意的是,在脱髓鞘阶段,用 10 和 100mg/kg HCQ 治疗的组中 Olig2+细胞的比例很高,并且在髓鞘再生阶段呈下降趋势。然而,基于胼胝体区域中寡核苷酸 2+/总细胞的百分比,各组在第 I 期和第 II 期之间没有显著差异。在第 I 期,用 10mg/kg HCQ 治疗的组中 PDGFR-α+细胞的数量显著增加(p 值<0.05)。考虑到 100mg/kg HCQ 组的 PDGFR-α 水平最高,LFB 染色中的髓鞘修复水平也最高,因此可以推断它是诱导 OPC 增殖和迁移的最有效剂量。