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: Ecologic correlations suggest that higher intake of saturated fat and lower intake of polyunsaturated fat might increase the risk of multiple sclerosis (MS), but the results of case-control studies have been inconsistent. Because no prospective data are available, the authors examined these associations in two large cohorts, the Nurses' Health Study, which consisted of 92,422 women with 14 years of follow-up (1980-1994) and the Nurses' Health Study II, which consisted of 95,389 women with 4 years of follow-up (1991-1995). They documented 195 new cases of MS. The pooled multivariate relative risks comparing women in the highest quintile with those in the lowest were 1.1 (95% confidence interval: 0.7, 1.7) for total fat, 0.7 (95% confidence interval: 0.5, 1.2) for animal fat, 1.2 (95% confidence interval: 0.7, 2.1) for vegetable fat, 0.8 (95% confidence interval: 0.5, 1.3) for saturated fat, 1.1 (95% confidence interval: 0.7, 1.7) for monounsaturated fat, 1.7 (95% confidence interval 1.0, 2.8) for n-6 polyunsaturated fat, 1.3 (95% confidence interval: 0.8, 2.0) for trans unsaturated fat, and 0.7 (95% confidence interval: 0.4, 1.1) for cholesterol. Omega-3 fatty acids from fish were also unrelated to risk. However, the authors observed a nonsignificantly lower risk of MS for a higher intake of linolenic acid. These findings do not support relations between intakes of total fat or major specific types of fat and the risk of MS.American Journal of Epidemiology 01/2001; 152(11):1056-64. · 4.78 Impact Factor
- Journal of Nutrition 10/1952; 48(1):41-7. · 4.20 Impact Factor
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ABSTRACT: In multiple sclerosis, demyelination of the CNS axons is associated with axonal injury and degeneration, which is now accepted as the major cause of neurological disability in the disease. Although the kinetics and the extent of axonal damage have been described in detail, the mechanisms by which it occurs are as yet unclear; one suggestion is failure of remyelination. The goal of this study was to test the hypothesis that failure of prompt remyelination contributes to axonal degeneration following demyelination. Remyelination was inhibited by exposing the brain to 40 Gy of X-irradiation prior to cuprizone intoxication and this resulted in a significant increase in the extent of axonal degeneration and loss compared to non-irradiated cuprizone-fed mice. To exclude the possibility that this increase was a consequence of the X-irradiation and to highlight the significance of remyelination, we restored remyelinating capacity to the X-irradiated mouse brain by transplanting of GFP-expressing embryo-derived neural progenitors. Restoring the remyelinating capacity in these mice resulted in a significant increase in axon survival compared to non-transplanted, X-irradiated cuprizone-intoxicated mice. Our results support the concept that prompt remyelination protects axons from demyelination-associated axonal loss and that remyelination failure contributes to the axon loss that occurs in multiple sclerosis.Brain 07/2008; 131(Pt 6):1464-77. · 9.92 Impact Factor