The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
Progesterone and its metabolites increase myelin basic protein expression in organotypic slice cultures of rat cerebellum
Abstract
We have previously shown that progesterone (PROG) is synthesized by Schwann cells and promotes myelin formation in the peripheral nervous system (PNS). We now report that this neurosteroid also stimulates myelination in organotypic slice cultures of 7‐day‐old (P7) rat and mouse cerebellum. Myelination was evaluated by immunofluorescence analysis of the myelin basic protein (MBP). After 7 days in culture (7DIV), we found that adding PROG (2–5 × 10−5 M) to the culture medium caused a fourfold increase in MBP expression when compared to control slices. The effect of PROG on MBP expression involves the classical intracellular PROG receptor (PR): the selective PR agonist R5020 significantly increased MBP expression and the PR antagonist mifepristone (RU486) completely abolished the effect of PROG on this MBP expression. Moreover, treatment of P7‐cerebellar slice cultures from PR knockout (PRKO) mice with PROG had no significant effect on MBP expression. PROG was metabolized in the cerebellar slices to 5α‐dihydroprogesterone (5α‐DHP) and to the GABA A receptor‐active metabolite 3α,5α‐tetrahydroprogesterone (3α,5α‐THP, allopregnanolone). The 5α‐reductase inhibitor L685‐273 partially inhibited the effect of PROG, and 3α,5α‐THP (2–5 × 10−5 M) significantly stimulated the MBP expression, although to a lesser extent than PROG. The increase in MBP expression by 3α,5α‐THP involved GABA A receptors, as it could be inhibited by the selective GABA A receptor antagonist bicuculline. These findings suggest that progestins stimulate MBP expression and consequently suggest an increase in CNS myelination via two signalling systems, the intracellular PR and membrane GABA A receptors, and they confirm a new role of GABA A receptors in myelination.
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Cites
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Progesterone synthesis and myelin formation by Schwann cells
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Neurosteroids: Biosynthesis of Pregnenolone and Progesterone in Primary Cultures of Rat Glial Cells*
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Neurosteroid regulation of central nervous system development
Mellon, S. H. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.04.011 · Cited by 209
Marx, C. E., Keefe, R. S. E., Buchanan, R. W., Hamer, R. M., Kilts, J. D., Bradford, D. W., Strauss, J. L., Naylor, J. C., Payne, V. M., Lieberman, J. A., et al. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.26 · Cited by 193
Progesterone increases oligodendroglial cell proliferation in rat cerebellar slice cultures
Ghoumari, A. M., Baulieu, E. E., & Schumacher, M. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.05.023 · Cited by 161
Self-citationProgesterone and Nestorone Facilitate Axon Remyelination: A Role for Progesterone Receptors
Hussain, R., El-Etr, M., Gaci, O., Rakotomamonjy, J., Macklin, W. B., Kumar, N., Sitruk-Ware, R., Schumacher, M., & Ghoumari, A. M. (2011) · Endocrinology · doi:10.1210/en.2011-1219 · Cited by 123
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Metadata
- Authors
- Ghoumari, A. M., Ibanez, C., El‐Etr, M., Leclerc, P., Eychenne, B., O'Malley, B. W., Baulieu, E. E., & Schumacher, M.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2003-07-28
- Volume
- 86
- Issue
- 4
- Pages
- 848-859
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1588928891
- Cited by
- 291
- References
- 65
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- closed
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- Ghoumari, A. M., Ibanez, C., El‐Etr, M., Leclerc, P., Eychenne, B., O'Malley, B. W., Baulieu, E. E., & Schumacher, M. (2003). Progesterone and its metabolites increase myelin basic protein expression in organotypic slice cultures of rat cerebellum. Journal of Neurochemistry. https://doi.org/10.1046/j.1471-4159.2003.01881.x
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