Dietary vitamin D3 supplements reduce demyelination in the cuprizone model.
Vitamin D is emerging as a probably important environmental risk factor in multiple sclerosis, affecting both susceptibility and disease progression. It is not known to what extent this effect is due to a modulation of peripheral lymphocyte function, or to intrathecal effects of vitamin D. We invest...
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doaj-631f78259e574a55808e18c4577055bf2020-11-25T00:07:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01610e2626210.1371/journal.pone.0026262Dietary vitamin D3 supplements reduce demyelination in the cuprizone model.Stig WergelandØivind TorkildsenKjell-Morten MyhrLage AksnesSverre Jarl MørkLars BøVitamin D is emerging as a probably important environmental risk factor in multiple sclerosis, affecting both susceptibility and disease progression. It is not known to what extent this effect is due to a modulation of peripheral lymphocyte function, or to intrathecal effects of vitamin D. We investigated the effect of dietary vitamin D3 content on de/remyelination in the cuprizone model, which is a well established toxic model of demyelination, with no associated lymphocyte infiltration. The mice received diets either deficient of (<50 IU/kg), or supplemented with low (500 IU/kg), high (6200 IU/kg) or very high (12500 IU/kg) amounts of vit D3. Cuprizone (0.2%) was added to the diet for six weeks, starting two weeks after onset of the experimental diets. Mouse brain tissue was histopathologically evaluated for myelin and oligodendrocyte loss, microglia/macrophage activation, and lymphocyte infiltration after six weeks of cuprizone exposure, and two weeks after discontinuation of cuprizone exposure. High and very high doses of vitamin D3 significantly reduced the extent of white matter demyelination (p = 0.004) and attenuated microglia activation (p = 0.001). No differences in the density of oligodendrocytes were observed between the diet groups. Two weeks after discontinuation of cuprizone exposure, remyelination was only detectable in the white matter of mice receiving diets deficient of or with low vitamin D3 content. In conclusion, high dietary doses of vitamin D3 reduce the extent of demyelination, and attenuate microglia activation and macrophage infiltration in a toxic model of demyelination, independent of lymphocyte infiltration.http://europepmc.org/articles/PMC3197632?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Stig Wergeland Øivind Torkildsen Kjell-Morten Myhr Lage Aksnes Sverre Jarl Mørk Lars Bø |
spellingShingle |
Stig Wergeland Øivind Torkildsen Kjell-Morten Myhr Lage Aksnes Sverre Jarl Mørk Lars Bø Dietary vitamin D3 supplements reduce demyelination in the cuprizone model. PLoS ONE |
author_facet |
Stig Wergeland Øivind Torkildsen Kjell-Morten Myhr Lage Aksnes Sverre Jarl Mørk Lars Bø |
author_sort |
Stig Wergeland |
title |
Dietary vitamin D3 supplements reduce demyelination in the cuprizone model. |
title_short |
Dietary vitamin D3 supplements reduce demyelination in the cuprizone model. |
title_full |
Dietary vitamin D3 supplements reduce demyelination in the cuprizone model. |
title_fullStr |
Dietary vitamin D3 supplements reduce demyelination in the cuprizone model. |
title_full_unstemmed |
Dietary vitamin D3 supplements reduce demyelination in the cuprizone model. |
title_sort |
dietary vitamin d3 supplements reduce demyelination in the cuprizone model. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
description |
Vitamin D is emerging as a probably important environmental risk factor in multiple sclerosis, affecting both susceptibility and disease progression. It is not known to what extent this effect is due to a modulation of peripheral lymphocyte function, or to intrathecal effects of vitamin D. We investigated the effect of dietary vitamin D3 content on de/remyelination in the cuprizone model, which is a well established toxic model of demyelination, with no associated lymphocyte infiltration. The mice received diets either deficient of (<50 IU/kg), or supplemented with low (500 IU/kg), high (6200 IU/kg) or very high (12500 IU/kg) amounts of vit D3. Cuprizone (0.2%) was added to the diet for six weeks, starting two weeks after onset of the experimental diets. Mouse brain tissue was histopathologically evaluated for myelin and oligodendrocyte loss, microglia/macrophage activation, and lymphocyte infiltration after six weeks of cuprizone exposure, and two weeks after discontinuation of cuprizone exposure. High and very high doses of vitamin D3 significantly reduced the extent of white matter demyelination (p = 0.004) and attenuated microglia activation (p = 0.001). No differences in the density of oligodendrocytes were observed between the diet groups. Two weeks after discontinuation of cuprizone exposure, remyelination was only detectable in the white matter of mice receiving diets deficient of or with low vitamin D3 content. In conclusion, high dietary doses of vitamin D3 reduce the extent of demyelination, and attenuate microglia activation and macrophage infiltration in a toxic model of demyelination, independent of lymphocyte infiltration. |
url |
http://europepmc.org/articles/PMC3197632?pdf=render |
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