Cited by 159Nerve injury and regenerationVitamin D Research StudiesPeripheral Neuropathies and Disorders

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Cholecalciferol (Vitamin D3) Improves Myelination and Recovery after Nerve Injury

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Chabas, Jean-Francois, Stephan, Delphine, Marqueste, Tanguy, Garcia, Stephane, Lavaut, Marie-Noelle, Nguyen, Catherine, Legre, Regis, Khrestchatisky, Michel, Decherchi, Patrick, Feron, Francois·2013·PLoS ONE

DOI 10.1371/journal.pone.0065034PMC PMC3669361

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Abstract

Previously, we demonstrated i) that ergocalciferol (vitamin D2) increases axon diameter and potentiates nerve regeneration in a rat model of transected peripheral nerve and ii) that cholecalciferol (vitamin D3) improves breathing and hyper-reflexia in a rat model of paraplegia. However, before bringing this molecule to the clinic, it was of prime importance i) to assess which form - ergocalciferol versus cholecalciferol - and which dose were the most efficient and ii) to identify the molecular pathways activated by this pleiotropic molecule. The rat left peroneal nerve was cut out on a length of 10 mm and autografted in an inverted position. Animals were treated with either cholecalciferol or ergocalciferol, at the dose of 100 or 500 IU/kg/day, or excipient (Vehicle), and compared to unlesioned rats (Control). Functional recovery of hindlimb was measured weekly, during 12 weeks, using the peroneal functional index. Ventilatory, motor and sensitive responses of the regenerated axons were recorded and histological analysis was performed. In parallel, to identify the genes regulated by vitamin D in dorsal root ganglia and/or Schwann cells, we performed an in vitro transcriptome study. We observed that cholecalciferol is more efficient than ergocalciferol and, when delivered at a high dose (500 IU/kg/day), cholecalciferol induces a significant locomotor and electrophysiological recovery. We also demonstrated that cholecalciferol increases i) the number of preserved or newly formed axons in the proximal end, ii) the mean axon diameter in the distal end, and iii) neurite myelination in both distal and proximal ends. Finally, we found a modified expression of several genes involved in axogenesis and myelination, after 24 hours of vitamin supplementation. Our study is the first to demonstrate that vitamin D acts on myelination via the activation of several myelin-associated genes. It paves the way for future randomised controlled clinical trials for peripheral nerve or spinal cord repair.

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1 retracted

Retracted Paper - Low-Dose Vitamin D Prevents Muscular Atrophy and Reduces Falls and Hip Fractures in Women after Stroke: A Randomized Controlled Trial
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Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
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Vitamin D
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Vitamin D2Is Much Less Effective than Vitamin D3in Humans
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The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease
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“immune disease [66].”
THE INFLUENCE OF THE PROINFLAMMATORY CYTOKINE, OSTEOPONTIN, ON AUTOIMMUNE DEMYELINATING DISEASE
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Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons
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RETRACTED: Vitamin D and rosuvastatin obliterate peripheral neuropathy in a type-2 diabetes model through modulating Notch1, Wnt-10α, TGF-β and NRF-1 crosstalk
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Authors: Chabas, J.-F., Stephan, D., Marqueste, T., Garcia, S., Lavaut, M.-N., Nguyen, C., Legre, R., Khrestchatisky, M., Decherchi, P., & Feron, F.
Affiliations: Centre National de la Recherche Scientifique (FR)
Inserm (FR)
Corresponding author: Decherchi, Patrick
Feron, Francois
ORCID: Stephan, Delphine
Marqueste, Tanguy
Nguyen, Catherine
Khrestchatisky, Michel
Decherchi, Patrick
Feron, Francois
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2013-05-31
Volume: 8
Issue: 5
Pages: e65034
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0065034
PMC: PMC3669361
OpenAlex: W2063567891
Cited by: 159
References: 70
Citations by year: 2026: 8 · 2025: 10 · 2024: 12 · 2023: 12 · 2022: 11 · 2021: 17 · 2020: 22 · 2019: 15 · 2018: 13 · 2017: 11 · 2016: 9 · 2015: 14 · 2014: 4 · 2013: 1
FWCI: 4.58
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, other-oa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
HAL (submittedVersion, cc-by)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Aix-Marseille Université
Centre National de la Recherche Scientifique
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Vitamin D Research Studies
Health Sciences › Medicine › Clinical Neurology › Peripheral Neuropathies and Disorders
Keywords: vitamin D3, vitamin D2, peripheral nerve regeneration, nerve transection, myelination, Schwann cells, dorsal root ganglia, axon diameter, functional recovery, peroneal nerve, transcriptome, axogenesis, spinal cord repair
MeSH terms: Animals, Axons, Cholecalciferol, Gene Expression Regulation, Male, Motor Activity, Myelin Sheath, Nerve Regeneration, Organ Size, Peroneal Nerve, Time Factors, Signal Transduction, Muscle, Skeletal, Muscle Fibers, Skeletal, Gene Expression Profiling, Rats, Gene Regulatory Networks, Neurogenesis, Peripheral Nerve Injuries

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Cholecalciferol (Vitamin D3) Improves Myelination and Recovery after Nerve Injury

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