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Cholecalciferol (Vitamin D3) Improves Myelination and Recovery after Nerve Injury
Open accessAbstract
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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“Vitamin D has also been shown to modify the expression of several genes involved in axogenesis and myelination [173].”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [173]
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Metadata
- 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
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-05-31
- Volume
- 8
- Issue
- 5
- Pages
- e65034
- ISSN
- 1932-6203 (ISSN-L)
- 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
- 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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