Abstract
Several studies in the last decade demonstrated that progestogens play an important role in the biology of Schwann cells, the main neuroglial cells of the peripheral nervous system. Since a recent study showed that the S42 rat Schwann cell line expressed membrane progesterone receptors (mPRs), members of the PAQR family, in this study, we examined mPR expression in a more physiological model, primary rat Schwann cells. We demonstrated that primary rat Schwann cells show a different pattern of mPR expression compared to the previously studied model; mPRα (PAQR7) and β (PAQR8) isoforms were the major mPR members identified, with different sub-cellular localizations. Activation of the nuclear progesterone receptor (PR) with the specific agonist R5020 upregulated mPR expression, while activation of mPRs with the specific agonist Org OD 02-0 changed their sub-cellular localization. An in-depth analysis revealed additional effects of mPR activation, such as AKT activation, reduced expression of the myelin-associated glycoprotein (MAG), morphological changes, altered expression of several Schwann cell differentiation markers, and increased Schwann cell migration and proliferation. In conclusion, we identified mPRα and mPRβ in primary rat Schwann cells, and our findings suggest a putative role for mPRs in the regulation of Schwann cell migration, proliferation, and differentiation. Therefore, mPRs are a potential pharmacological target for Schwann cell–related disorders and neurodegenerative diseases, especially those in which Schwann cell–mediated axon remyelination is desirable.
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Abbreviations
- SCs:
-
Schwann cells;
- PNS:
-
peripheral nervous system;
- P4:
-
progesterone;
- DHP:
-
dihydroprogesterone;
- ALLO:
-
allopregnanolone;
- GABAA-R:
-
GABAA receptor;
- PMP22:
-
peripheral myelin protein of 22 KDa;
- PR:
-
progesterone receptor;
- P0:
-
myelin protein zero;
- mPRs:
-
membrane progesterone receptors;
- PAQR:
-
progestin and AdipoQ receptor;
- cAMP:
-
cyclic AMP;
- MAG:
-
myelin-associated glycoprotein;
- 02-0:
-
Org OD 02-0;
- GNX:
-
ganaxolone;
- DMEM:
-
Dulbecco’s modified Eagle’s medium;
- FBS:
-
fetal bovine serum;
- BSA:
-
bovine serum albumin;
- BrdU:
-
5-bromo-2′-deoxyuridine;
- Veh:
-
vehicle
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Acknowledgments
The authors would like to thank Valentina Melfi for her contribution in the preparation of the final version of this article.
Funding
This work was supported by a grant from MIUR “Progetto Eccellenza” and by institutional funding from the University of Milan to V.M. The funding source was not involved in study design, collection, analysis, and interpretation of data, nor in the writing of the report and in the decision to submit the article for publication.
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Castelnovo, L.F., Caffino, L., Bonalume, V. et al. Membrane Progesterone Receptors (mPRs/PAQRs) Differently Regulate Migration, Proliferation, and Differentiation in Rat Schwann Cells. J Mol Neurosci 70, 433–448 (2020). https://doi.org/10.1007/s12031-019-01433-6
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DOI: https://doi.org/10.1007/s12031-019-01433-6