Effects of dietary intervention on MRI activity, de- and remyelination in the cuprizone model for demyelination.
ABSTRACT Whether differences in diet composition may influence demyelinating diseases remains controversial. The aim of this study was to analyse if diets with a different composition of polyunsaturated fatty acids (PUFAs) could influence demyelination and remyelination in cuprizone fed mice, a widely used animal model for de- and remyelination. C57Bl/6 mice were fed with 0.2% cuprizone on three different diets. The diets consisted of the same ingredients, except the lipid source, which came from 1) salmon fillets rich in marine n-3 polyunsaturated fatty acids (PUFAs), 2) cod liver oil rich in marine n-3 PUFAs, or 3) a control diet containing soybean oil rich in n-6 PUFAs. After 5 weeks of cuprizone treatment, the mice given salmon-cuprizone had significantly less hyperintense lesion volume on brain magnetic resonance imaging (MRI) than the two other groups (P<0.0005). After 6 weeks of cuprizone treatment, the salmon-cuprizone group had less demyelination in the corpus callosum, as measured with luxol fast blue (LFB) (P<0.0005) and anti-proteolipid protein (PLP) (P=0.014). The salmon-cuprizone group also had enhanced remyelination compared to the cod liver oil-cuprizone group (LFB; P=0.003, PLP; P=0.018). This study indicates that a fish rich diet may offer a protective role in demyelination. The source of N-3 PUFAs, or other components in the fish, may be important, as no effect of a cod liver oil based diet was observed. This may be of importance related to the discrepant results in dietary intervention studies for demyelinating diseases.
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ABSTRACT: 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.PLoS ONE 01/2011; 6(10):e26262. · 4.09 Impact Factor