Melatonin ameliorates astrogliosis and microgliosis in a cuprizone demyelinating mouse model

Background and purpose: Several investigations have reported that melatonin is involved in the amelioration of the inflammatory process, improvement of myelin function, and regeneration in the central nervous system (CNS). The current study aimed to evaluate the protective effect of melatonin in cuprizone (CPZ)-induced myelin damage in the corpus callosum (CC) and explore the plausible underlying mechanisms of remyelination capacity and/or neuroprotection. Method: We administered cuprizone in chow either alone daily for 6 weeks or combined with simultaneously applied melatonin intra-peritoneal injections. we studied demyelination by LFB staining, oligodendrocyte staining using anti-Olig2 or anti-APC antibodies. In addition, we visualized microgliosis and astrocytosis by staining with anti-Iba-1 and anti-GFAP antibodies. Furthermore, we study the effect of melatonin on mRNA expression of Musashi-1, Hes-1 and Notch-1 genes. Results: Our data showed that cuprizone intoxication caused a significant oligodendrocyte loss, demyelination, and reactive gliosis in CC. Administration of melatonin prevented the demyelination in CC as determined by Luxol fast blue staining. Furthermore, we found that the melatonin significantly suppressed the cuprizoneinduced microgliosis and astrocytosis. while the frequency of oligodendrocytes (Olig2+) was significantly enhanced in the CC after melatonin administration. In addition, melatonin significantly modulated Musashi1, Hes1, and Notch1 mRNA expression in the CC of mice. Conclusion: These results provide evidence that melatonin abolishes destructive cuprizone effects in the mouse corpus callosum by restoring oligodendrocyte generation, remyelination, and decreasing astrogliosis and microgliosis.