Mineralocorticoid receptor knockout in Schwann cells alters myelin sheath thickness

in Journal of Endocrinology
Authors:
Alberto González-Mayoral INSERM UMRS 1124 (T3S), Faculty of Basic and Biomedical Sciences, Université Paris Cité, Paris, France
Paris Brain Institue-Institut du Cerveau, CNRS UMR7225, INSERM U1127, Hôpital de la Pitié Salpêtrière, Paris, France

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Axel Eid INSERM UMRS 1124 (T3S), Faculty of Basic and Biomedical Sciences, Université Paris Cité, Paris, France
INSERM UMR 1195 (DHNS), Faculty of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France

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Razmig Derounian INSERM UMRS 1124 (T3S), Faculty of Basic and Biomedical Sciences, Université Paris Cité, Paris, France

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Virginia Sofia Campanella INSERM UMRS 1124 (T3S), Faculty of Basic and Biomedical Sciences, Université Paris Cité, Paris, France

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Andreia da Silva Ramos INSERM UMRS 1124 (T3S), Faculty of Basic and Biomedical Sciences, Université Paris Cité, Paris, France

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Romy El Khoury INSERM UMRS 1124 (T3S), Faculty of Basic and Biomedical Sciences, Université Paris Cité, Paris, France

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Charbel Massaad INSERM UMRS 1124 (T3S), Faculty of Basic and Biomedical Sciences, Université Paris Cité, Paris, France

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Damien Le Menuet INSERM UMRS 1124 (T3S), Faculty of Basic and Biomedical Sciences, Université Paris Cité, Paris, France

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https://orcid.org/0000-0002-0802-7190

Correspondence should be addressed to D Le Menuet: damien.le-menuet@inserm.fr
DOI:
https://doi.org/10.1530/JOE-22-0334
Volume/Issue:
Volume 258: Issue 2
Article Type:
Research Article
Article ID:
e220334
Online Publication Date:
12 Jul 2023
Copyright:
© the author(s) 2023
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Myelination allows fast and synchronized nerve influxes and is provided by Schwann cells (SCs) in the peripheral nervous system. Glucocorticoid hormones are major regulators of stress, metabolism and immunity affecting all tissues. They act by binding to two receptors, the low-affinity glucocorticoid receptor (GR) and the high-affinity mineralocorticoid receptor (MR). Little is known about the effect of glucocorticoid hormones on the PNS, and this study focuses on deciphering the role of MR in peripheral myelination. In this work, the presence of a functional MR in SCs is demonstrated and the expression of MR protein in mouse sciatic nerve SC is evidenced. Besides, knockout of MR in SC (SCMRKO using Cre-lox system with DesertHedgeHog (Dhh) Cre promoter) was undertaken in mice. SCMRKO was not associated with alterations of performance in motor behavioral tests on 2- to 6-month-old male mice compared to their controls. No obvious modifications of myelin gene expression or MR signaling gene expression were observed in the SCMRKO sciatic nerves. Nevertheless, Gr transcript and GR protein amounts were significantly increased in SCMRKO nerves compared to controls, suggesting a possible compensatory effect. Besides, an increase in myelin sheath thickness was noted for axons with perimeters larger than 15 µm in SCMRKO illustrated by a significant 4.5% reduction in g-ratio (axon perimeter/myelin sheath perimeter). Thus, we defined MR as a new player in peripheral system myelination and in SC homeostasis.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© the author(s) 2023
Article ID:
e220334
Article Type:
Research Article
Received Date:
09 May 2023
Accepted Date:
17 May 2023
Print Publication Date:
01 Aug 2023
Online Publication Date:
12 Jul 2023
Keywords:
peripheral nervous system; Schwann cells; glucocorticoids; mineralocorticoid receptor

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