Cited by 51Neurogenesis and neuroplasticity mechanismsMultiple Sclerosis Research StudiesEstrogen and related hormone effects

Sexual dimorphism of oligodendrocytes is mediated by differential regulation of signaling pathways

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Swamydas, Muthulekha, Bessert, Denise, Skoff, Robert·2009·Journal of Neuroscience Research

Abstract

Sexual dimorphism of white matter has not been considered important, the assumption being that sex hormones are not essential for glial development. We recently showed exogenous hormones in vivo differentially regulate in male and female rodents the life span of oligodendrocytes (Olgs) and amount of myelin (Cerghet et al. [2006] J. Neurosci. 26:1439-1447). To determine which hormones regulate male and female Olg development, we prepared enriched Olg cultures grown in serum-free medium with estrogen (E2), progesterone (P2), and dihydrotestosterone (DHT) or their combinations. P2 significantly increased the number of Olgs in both sexes, but more so in females; E2 had minor effects on Olg numbers; and DHT reduced Olgs numbers in both sexes, but more so in females. Combinations of hormones affected Olg numbers differently from single hormones. The change in Olg numbers was due to changes not in proliferation but rather in survival. P2 increased pAKT by many-fold, but MAPK levels were unchanged, indicating that activation of the Akt pathway by P2 is sufficient to regulate Olg differentiation. DHT reduced pAkt in both sexes but differentially increased pMAPK in males and decreased it in females. Stressing Olgs reveals that both sexes are protected by P2, but females are slightly better protected than males. Females always showed greater differences than males regarding changes in Olg numbers and in signaling molecules. Given the greater fluctuation of neurosteroids in women than in men and the higher incidence of multiple sclerosis (MS) in women, these sexually dimorphic differences may contribute to differences in male and female MS lesions.

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  • Female and male oligodendrocyte levels and myelination are differentially sensitive to steroids, such as progesterone and dihydrotestosterone.

    “Female and male oligodendrocyte levels and myelination are differentially sensitive to steroids, such as progesterone and dihydrotestosterone (Swamydas et al., 2009).”

    From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Swamydas et al., 2009

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  1. Vitry S Avellana-Adalid V Hardy R Lachapelle F Baron-Van Evercooren A Mouse oligospheres: from pre-progenitors to functional oligodendrocytes J Neurosci Res 1999 58 735 751 10583906

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Authors
Swamydas, M., Bessert, D., & Skoff, R.
Affiliations
Wayne State University (US)
Corresponding author
Skoff, Robert
Venue
Journal of Neuroscience Research
Publisher
Wiley
Published
2008-12-15
Volume
87
Issue
15
Pages
3306-3319
ISSN
  • 0360-4012 (ISSN-L)
  • 1097-4547
OpenAlex
W2102118606
Cited by
51
References
67
Citations by year
2026: 2 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 4 · 2020: 2 · 2019: 6 · 2017: 4 · 2016: 3 · 2014: 1 · 2013: 1 · 2012: 2
FWCI
0.71
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R01NS038236)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
sexual dimorphism, oligodendrocytes, sex hormones, progesterone, estrogen, dihydrotestosterone, Akt signaling, MAPK signaling, oligodendrocyte survival, myelination, white matter, multiple sclerosis, neurosteroids, sex differences
MeSH terms
Animals, Cell Differentiation, Cell Survival, Cells, Cultured, Central Nervous System, Estrogens, Female, Male, Mice, Inbred CBA, Oligodendroglia, Progesterone, Sex Characteristics, Gonadal Steroid Hormones, Dihydrotestosterone, Stem Cells, Stress, Physiological, Signal Transduction, Causality, Culture Media, Serum-Free, Cytoprotection, Cell Proliferation, Proto-Oncogene Proteins c-akt, Mice

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