Effect of melatonin on oligodendrocyte maturation and differentiation in corpus callosum of septic neonatal rats / 中华急诊医学杂志

ABSTRACT

Objective:To investigate the effect of melatonin on oligodendrocyte maturation and differentiation in corpus callosum of septic neonatal rats induced by systemic lipopolysaccharide (LPS) injection.Methods:Sprague-Dawley rats were randomly allocated into the control group, septic experimental group, and melatonin group. In the septic experimental group, rats were intraperitoneally administrated with lipopolysaccharide (LPS) (1 mg/kg). In the melatonin group, melatonin was intraperitoneally administered (10 mg/kg) at 0.5 h after LPS injection. The expression level of IL-6, olig1, olig2, and the MAG protein were detected by Western blot at different time points in the three groups. BV-2 cells were used in vitro. For drug administration, the effect of LPS, melatonin and melatonin receptor antagonist, luzindole, on IL-6 expression in BV-2 microglia cell was determined by Western blot. The medium of BV2 cell were collected to treat primary OPCs. The expression level of olig1, olig2 and MAG protein in primary OPCs were detected by Western blot. SPSS 20.0 statistical software was used for analysis, and the data were analyzed by one-way ANOVA and two-way ANOVA. Differences were considered to be statistically significantly if P<0.05. Result:Compared with the LPS group, the expression of IL-6 was significantly decreased in the corpus callosum at 6 h, l d, and 3 d in the melatonin group ( P<0.05). The expression of olig1, olig2 and MAG protein were increased at day 7, 14, and 28 in the melatonin group compared with the LPS group ( P<0.05). In vitro the expressions of IL-6 was significantly increased after LPS treatment ( P<0.05), but was decreased in the LPS+melatonin treatment group ( P<0.05). After treatment with melatonin receptor inhibitor, luzindole, the expressions level of IL-6 was increased ( P<0.05). The expression of olig1, olig2 and MAG protein were decreased with conditioned medium in the LPS BV2 cell group than the control group in the primary OPCs ( P<0.05). However, those were increased with conditioned medium in the LPS+melatonin BV2 cell group than the LPS group ( P<0.05). Conclusions:Melatonin may inhibit the inflammation response in the corpus callosum through its receptor, and may promote the maturation and differentiation of oligodendrocyte, suggesting that melatonin may have therapeutic effect on neuroinflammation and axonal hypomyelination on PWM in septic neonatal rats.