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Melatonin promotes oligodendroglial maturation of injured white matter in neonatal rats

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Paul Olivier, Romain H Fontaine, Gauthier Loron, Juliette Van Steenwinckel, Valérie Biran, Véronique Massonneau, Angela Kaindl, Jeremie Dalous, Christiane Charriaut-Marlangue, Marie-Stéphane Aigrot, Julien Pansiot, Catherine Verney, Pierre Gressens, Olivier Baud

Original languageEnglish
Article numbere7128
Pages (from-to)N/A
Number of pages13
JournalPLoS ONE
Issue number9
Publication statusPublished - 22 Sep 2009

King's Authors



To investigate the effects of melatonin treatment in a rat model of white matter damage (WMD) in the developing brain. Additionally, we aim to delineate the cellular mechanisms of melatonin effect on the oligodendroglial cell lineage.


A unilateral ligation of the uterine artery in pregnant rat at the embryonic day 17 induces fetal hypoxia and subsequent growth restriction (GR) in neonatal pups. GR and control pups received a daily intra-peritoneal injection of melatonin from birth to post-natal day (P) 3.


Melatonin administration was associated with a dramatic decrease in microglial activation and astroglial reaction compared to untreated GR pups. At P14, melatonin prevented white matter myelination defects with an increased number of mature oligodendrocytes (APC-immunoreactive) in treated GR pups. Conversely, melatonin was not found to be associated with an increased density of total oligodendrocytes (Olig2-immunoreactive), suggesting that melatonin is able to promote oligodendrocyte maturation but not proliferation. These effects appear to be melatonin-receptor dependent and were reproduced in vitro.


These data suggest that melatonin has a strong protective effect on developing damaged white matter through decreased microglial activation and oligodendroglial maturation leading to a normalization of the myelination process. Consequently, melatonin should be a considered as an effective neuroprotective candidate not only in perinatal brain damage but also in inflammatory and demyelinating diseases observed in adults.

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