i-Brain Team- UMR INSERM U1253, UFR de Médecine, Université de Tours, Bâtiment Thérèse Planiol, 10 Bd Tonnellé, BP 3223, 37032, Tours Cedex 1, France.
Neonatology Unit, CHRU de Tours, Tours, France.
Sci Rep. 2021 Nov 12;11(1):22167. doi: 10.1038/s41598-021-01746-w.
Melatonin has shown promising neuroprotective effects due to its anti-oxidant, anti-inflammatory and anti-apoptotic properties, making it a candidate drug for translation to humans in conditions that compromise the developing brain. Our study aimed to explore the impact of prenatal melatonin in an inflammatory/infectious context on GABAergic neurons and on oligodendrocytes (OLs), key cells involved in the encephalopathy of prematurity. An inflammatory/infectious agent (LPS, 300 μg/kg) was injected intraperitoneally (i.p.) to pregnant Wistar rats at gestational day 19 and 20. Melatonin (5 mg/kg) was injected i.p. following the same schedule. Immunostainings focusing on GABAergic neurons, OL lineage and myelination were performed on pup brain sections. Melatonin succeeded in preventing the LPS-induced decrease of GABAergic neurons within the retrospenial cortex, and sustainably promoted GABAergic neurons within the dentate gyrus in the inflammatory/infectious context. However, melatonin did not effectively prevent the LPS-induced alterations on OLs and myelination. Therefore, we demonstrated that melatonin partially prevented the deleterious effects of LPS according to the cell type. The timing of exposure related to the cell maturation stage is likely to be critical to achieve an efficient action of melatonin. Furthermore, it can be speculated that melatonin exerts a modest protective effect on extremely preterm infant brains.
褪黑素具有抗氧化、抗炎和抗细胞凋亡作用，显示出有希望的神经保护作用，使其成为在发育中的大脑受损的情况下转化为人类的候选药物。我们的研究旨在探讨在炎症/感染环境下产前褪黑素对 GABA 能神经元和少突胶质细胞（OLs）的影响，OLs 是早产儿脑病的关键细胞。在妊娠第 19 天和第 20 天，向 Wistar 孕鼠腹腔内注射炎症/感染剂（LPS，300μg/kg）。根据相同的方案，腹腔内注射褪黑素（5mg/kg）。对幼鼠脑切片进行针对 GABA 能神经元、OL 谱系和髓鞘形成的免疫染色。褪黑素成功地防止了 LPS 诱导的逆行皮质 GABA 能神经元减少，并在炎症/感染环境中持续促进齿状回 GABA 能神经元。然而，褪黑素并不能有效地防止 LPS 诱导的 OL 和髓鞘形成的改变。因此，我们证明褪黑素根据细胞类型部分预防了 LPS 的有害作用。暴露的时间与细胞成熟阶段有关，这可能对褪黑素的有效作用至关重要。此外，可以推测褪黑素对极早产儿的大脑有适度的保护作用。
