Melatonin Promotes Oligodendroglial Maturation of Injured White Matter in Neonatal Rats
Open accessAbstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. INTERPRETATION: 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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Administration of melatonin promotes oligodendroglial maturation in the newborn rat with abnormal white matter related to fetal hypoxia.
“promotes oligodendroglial maturation in the newborn rat with abnormal white matter related to fetal hypoxia.105”
From Autism risk factors: genes, environment, and gene-environment interactions (2012) · cites this paper as [105]
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- Authors
- Olivier, P., Fontaine, R. H., Loron, G., Van Steenwinckel, J., Biran, V., Massonneau, V., Kaindl, A., Dalous, J., Charriaut-Marlangue, C., Aigrot, M.-S., Pansiot, J., Verney, C., Gressens, P., & Baud, O.
- Affiliations
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Baud, Olivier
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-09-22
- Volume
- 4
- Issue
- 9
- Pages
- e7128
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2742165
- OpenAlex
- W1966357480
- Cited by
- 119
- References
- 37
- Citations by year
- 2025: 3 · 2024: 7 · 2023: 5 · 2022: 11 · 2021: 17 · 2020: 6 · 2019: 8 · 2018: 4 · 2017: 7 · 2016: 6 · 2015: 7 · 2014: 9 · 2013: 9 · 2012: 9
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Update notices
- correction (2009-10-15)
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Ikaria
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique (UMR 7101)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- melatonin, oligodendrocyte maturation, white matter injury, fetal hypoxia, growth restriction, uterine artery ligation, myelination, microglial activation, astroglial reaction, APC, Olig2, neuroprotection, perinatal brain injury, melatonin receptors
- MeSH terms
- Animals, Animals, Newborn, Brain, Cells, Cultured, Immunohistochemistry, Melatonin, Microscopy, Fluorescence, Nerve Fibers, Myelinated, Oligodendroglia, RNA, Messenger, Time Factors, Rats, Sprague-Dawley, Gene Expression Regulation, Developmental, Cell Lineage, Rats
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