Cholecalciferol (vitamin D₃) improves myelination and recovery after nerve injury.

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 bring...

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Autores principales:	Jean-Francois Chabas, Delphine Stephan, Tanguy Marqueste, Stephane Garcia, Marie-Noelle Lavaut, Catherine Nguyen, Regis Legre, Michel Khrestchatisky, Patrick Decherchi, Francois Feron
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/605f5ed37d01487db45f645aa5ab6522
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spelling	oai:doaj.org-article:605f5ed37d01487db45f645aa5ab65222021-11-18T07:43:28ZCholecalciferol (vitamin D₃) improves myelination and recovery after nerve injury.1932-620310.1371/journal.pone.0065034https://doaj.org/article/605f5ed37d01487db45f645aa5ab65222013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23741446/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Previously, 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.Jean-Francois ChabasDelphine StephanTanguy MarquesteStephane GarciaMarie-Noelle LavautCatherine NguyenRegis LegreMichel KhrestchatiskyPatrick DecherchiFrancois FeronPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e65034 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jean-Francois Chabas Delphine Stephan Tanguy Marqueste Stephane Garcia Marie-Noelle Lavaut Catherine Nguyen Regis Legre Michel Khrestchatisky Patrick Decherchi Francois Feron Cholecalciferol (vitamin D₃) improves myelination and recovery after nerve injury.
description	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.
format	article
author	Jean-Francois Chabas Delphine Stephan Tanguy Marqueste Stephane Garcia Marie-Noelle Lavaut Catherine Nguyen Regis Legre Michel Khrestchatisky Patrick Decherchi Francois Feron
author_facet	Jean-Francois Chabas Delphine Stephan Tanguy Marqueste Stephane Garcia Marie-Noelle Lavaut Catherine Nguyen Regis Legre Michel Khrestchatisky Patrick Decherchi Francois Feron
author_sort	Jean-Francois Chabas
title	Cholecalciferol (vitamin D₃) improves myelination and recovery after nerve injury.
title_short	Cholecalciferol (vitamin D₃) improves myelination and recovery after nerve injury.
title_full	Cholecalciferol (vitamin D₃) improves myelination and recovery after nerve injury.
title_fullStr	Cholecalciferol (vitamin D₃) improves myelination and recovery after nerve injury.
title_full_unstemmed	Cholecalciferol (vitamin D₃) improves myelination and recovery after nerve injury.
title_sort	cholecalciferol (vitamin d₃) improves myelination and recovery after nerve injury.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/605f5ed37d01487db45f645aa5ab6522
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Cholecalciferol (vitamin D₃) improves myelination and recovery after nerve injury.

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