17beta‐estradiol protects oligodendrocytes from cytotoxicity induced cell death
Abstract
During pregnancy, changes in circulating levels of hormones, including estrogens, correlates with a significant decrease in the relapse incidence in women with Multiple Sclerosis (MS). In the present study, we demonstrate that both primary and cell line cultures of rat oligodendrocytes express the estrogen receptor (ER)‐α and ERβ estrogen receptors in the cytosol and nucleus, and that nuclear compartmentalization becomes more pronounced as the cells mature. Moreover, 17β‐estradiol significantly decreases the cytotoxic effects of the peroxynitrite generator 3‐(4‐morpholinyl)‐sydnonimine (SIN‐1) in both immature and mature oligodendrocytes in a dose dependent manner. This protective mechanism requires pretreatment with 17β‐estradiol and is blocked by ICI 182,780, a selective ERα/ERβ antagonist. These results strongly suggest that 17β‐estradiol protects oligodendrocytes against SIN‐1 mediated cytotoxicity through the activation of the estrogen receptors and provides new insights into the roles of the estrogen signaling pathways in myelin forming cells that are lost in demyelinating disorders.
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Sex hormones have been shown to have direct effects on oligodendrocyte proliferation and maturation as well as survival.
“In addition, sex hormones have been shown to have direct effects on oligodendrocyte proliferation and maturation 21, 33 as well as survival 20, 51.”
From SJL Mice Exposed to Cuprizone Intoxication Reveal Strain and Gender Pattern Differences in Demyelination (2009) · cites this paper as [51]
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Compston, A., & Coles, A. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08220-x · Cited by 1,743 · see citing works
Treatment of multiple sclerosis with the pregnancy hormone estriol
Sicotte, N. L., Liva, S. M., Klutch, R., Pfeiffer, P., Bouvier, S., Odesa, S., Wu, T. C. J., & Voskuhl, R. R. (2002) · Annals of Neurology · doi:10.1002/ana.10301 · Cited by 435 · see citing works
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Needham, B. D., Kaddurah-Daouk, R., & Mazmanian, S. K. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-00381-0 · Cited by 379 · see citing works
Azcoitia, I., Barreto, G. E., & Garcia-Segura, L. M. (2019) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2019.100787 · Cited by 125 · see citing works
Taylor, L. C., Gilmore, W., & Matsushima, G. K. (2009) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00230.x · Cited by 84 · see citing works
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Gonzalez, G. A., Hofer, M. P., Syed, Y. A., Amaral, A. I., Rundle, J., Rahman, S., Zhao, C., & Kotter, M. R. N. (2016) · Scientific Reports · doi:10.1038/srep31599 · Cited by 82 · see citing works
Sexual dimorphism of oligodendrocytes is mediated by differential regulation of signaling pathways
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- Authors
- Takao, T., Flint, N., Lee, L., Ying, X., Merrill, J., & Chandross, K. J.
- Affiliations
- Kōchi University (JP)
- Colgate University (US)
- Corresponding author
- Chandross, Karen J.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2004-03-22
- Volume
- 89
- Issue
- 3
- Pages
- 660-673
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2070648285
- Cited by
- 93
- References
- 2
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 5 · 2014: 2 · 2013: 6 · 2012: 4
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- estradiol, oligodendrocytes, estrogen receptor alpha, estrogen receptor beta, SIN-1, peroxynitrite, cytotoxicity, neuroprotection, fulvestrant, demyelinating disease, multiple sclerosis, estrogen signaling, myelination
- MeSH terms
- Fulvestrant, Animals, Cell Compartmentation, Cell Division, Cell Nucleus, Cells, Cultured, Cytosol, Estradiol, Estrogen Antagonists, Female, L-Lactate Dehydrogenase, Male, Molsidomine, Oligodendroglia, Receptors, Estrogen, RNA, Messenger, Cell Death, Rats, Sprague-Dawley, Cytoprotection, Nitric Oxide Donors, Estrogen Receptor alpha, Estrogen Receptor beta, Rats
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