Cited by 117Multiple Sclerosis Research StudiesNeurogenesis and neuroplasticity mechanismsNeuroinflammation and Neurodegeneration Mechanisms

Progesterone and nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex: Progesterone Receptor and Myelin Repair

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El-Etr, Martine, Rame, Marion, Boucher, Celine, Ghoumari, Abdel. M, Kumar, Narender, Liere, Philippe, Pianos, Antoine, Schumacher, Michael +1 more·2015·Glia

Abstract

Multiple Sclerosis affects mainly women and consists in intermittent or chronic damages to the myelin sheaths, focal inflammation, and axonal degeneration. Current therapies are limited to immunomodulators and antiinflammatory drugs, but there is no efficient treatment for stimulating the endogenous capacity of myelin repair. Progesterone and synthetic progestins have been shown in animal models of demyelination to attenuate myelin loss, reduce clinical symptoms severity, modulate inflammatory responses and partially reverse the age-dependent decline in remyelination. Moreover, progesterone has been demonstrated to promote myelin formation in organotypic cultures of cerebellar slices. In the present study, we show that progesterone and the synthetic 19-nor-progesterone derivative Nestorone® promote the repair of severe chronic demyelinating lesions induced by feeding cuprizone to female mice for up to 12 weeks. Progesterone and Nestorone increase the density of NG2(+) oligodendrocyte progenitor cells and CA II(+) mature oligodendrocytes and enhance the formation of myelin basic protein (MBP)- and proteolipid protein (PLP)-immunoreactive myelin. However, while demyelination in response to cuprizone was less marked in corpus callosum than in cerebral cortex, remyelination appeared earlier in the former. The remyelinating effect of progesterone was progesterone receptor (PR)-dependent, as it was absent in PR-knockout mice. Progesterone and Nestorone also decreased (but did not suppress) neuroinflammatory responses, specifically astrocyte and microglial cell activation. Therefore, some progestogens are promising therapeutic candidates for promoting the regeneration of myelin.

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  • Administration of progesterone promotes myelin regeneration in chronic demyelinated lesions in the corpus callosum of mice after cuprizone feeding.

    “and recently, the same group has shown that administration of progesterone promotes myelin regeneration in chronic demyelinated lesions in the corpus callosum of mice after being fed with cuprizone51.”

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Authors
El-Etr, M., Rame, M., Boucher, C., Ghoumari, A. M., Kumar, N., Liere, P., Pianos, A., Schumacher, M., & Sitruk-Ware, R.
Affiliations
  • UMR 788 Inserm and University Paris-Sud; 94276 Kremlin-Bicêtre France
  • Inserm (FR)
  • Population Council (US)
Venue
Glia
Publisher
Wiley
Published
2014-08-04
Volume
63
Issue
1
Pages
104-117
ISSN
0894-1491 (ISSN-L)
OpenAlex
W1494051921
Cited by
116
References
70
Citations by year
2026: 5 · 2025: 8 · 2024: 9 · 2023: 7 · 2022: 12 · 2021: 8 · 2020: 10 · 2019: 8 · 2018: 13 · 2017: 10 · 2016: 14 · 2015: 10 · 2013: 1
FWCI
8.41
Type
journal article
Language
en
Open access
Locations
  • Glia (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion)
Funders
National Institute of Child Health and Human Development (U54)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
progesterone, Nestorone, remyelination, demyelination, multiple sclerosis, cuprizone, corpus callosum, cerebral cortex, oligodendrocyte precursor cells, oligodendrocytes, myelin basic protein, proteolipid protein, progesterone receptor, neuroinflammation, astrocyte activation, microglial activation, progestogens
MeSH terms
Animals, Cerebral Cortex, Corpus Callosum, Cuprizone, Demyelinating Diseases, Disease Models, Animal, Myelin Basic Protein, Female, Mice, Inbred C57BL, Multiple Sclerosis, Myelin Sheath, Oligodendroglia, Progesterone, Stem Cells, Mice, Knockout, Myelin Proteolipid Protein

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