Contributions
Abstract: EP1419
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Experimental models
Dietary supplementation of vitamin D is commonly recommended to patients with multiple sclerosis. We recently suggested that high-dose of the hormonally active 1,25-dihydroxyvitamin-D3 (1,25D) promotes myelin repair in the cuprizone model for de- and remyelination. In the current study we investigated the effect of high-dose 1,25D on protein expression in mouse brain tissue during remyelination. c57Bl/6 mice were demyelinated with cuprizone for 7 weeks. The mice received intra-peritoneal injections of 1,25D or placebo twice a week, from week 6 and throughout week 10. Brain tissue samples were taken after 7 weeks (demyelination), after 8 weeks (1 week remyelination) and after 10 weeks (3 weeks of remyelination), and analysed using TMT-labeling and mass spectrometry based quantitative proteomics. We quantified 5062 proteins, of which 125 were significantly regulated in 1,25D treated mice. Calcium binding proteins (calretinin, S10A5, secretagogin) and mitochondrial proteins (NADH-ubiquinone oxidoreductase chain 3, Acyl-coenzyme A synthetase) were upregulated in the early remyelination phases. Calretinin, S10A5 and secretagogin expression levels were characterised using immunohistochemistry. Calretinin immunoreactivity was significantly increased in the lateral septal nuclei of 1,25D treated mice in the early remyelination phase. Our results indicate that vitamin D may affect remyelination by mechanisms involving calcium signaling and mitochondrial function.
Disclosure:
Agnes Elisabeth Nystad: has received an unrestricted grant from Novartis.
Eystein Oveland: nothing to disclose.
Frode Berven: nothing to disclose.
Kjell-Morten Myhr has served on scientific advisory boards for Novartis Norway, Biogen Idec, Genzyme and Roche; received speaker honoraria from Genzyme, Sanofi-Aventis, Novartis, Biogen Idec and Teva and received unrestricted research support from, Sanofi-Aventis, Novartis, Biogen Idec, and the Norwegian MS Society.
Øivind Torkildsen has served on scientific advisory boards for Genzyme, Merck-Serono and Biogen Idec and received speaker honoraria and travel grants from Genzyme, Merck-Serono, Novartis, and Biogen-Idec.
Stig Wergeland has received speaker honoraria, unrestricted research support and travel grants from Biogen Idec and Novartis and travel grant from Merck.
This work was funded by the Kristian Gerhard Jebsen Foundation and unrestricted grants from Novartis.
Abstract: EP1419
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Experimental models
Dietary supplementation of vitamin D is commonly recommended to patients with multiple sclerosis. We recently suggested that high-dose of the hormonally active 1,25-dihydroxyvitamin-D3 (1,25D) promotes myelin repair in the cuprizone model for de- and remyelination. In the current study we investigated the effect of high-dose 1,25D on protein expression in mouse brain tissue during remyelination. c57Bl/6 mice were demyelinated with cuprizone for 7 weeks. The mice received intra-peritoneal injections of 1,25D or placebo twice a week, from week 6 and throughout week 10. Brain tissue samples were taken after 7 weeks (demyelination), after 8 weeks (1 week remyelination) and after 10 weeks (3 weeks of remyelination), and analysed using TMT-labeling and mass spectrometry based quantitative proteomics. We quantified 5062 proteins, of which 125 were significantly regulated in 1,25D treated mice. Calcium binding proteins (calretinin, S10A5, secretagogin) and mitochondrial proteins (NADH-ubiquinone oxidoreductase chain 3, Acyl-coenzyme A synthetase) were upregulated in the early remyelination phases. Calretinin, S10A5 and secretagogin expression levels were characterised using immunohistochemistry. Calretinin immunoreactivity was significantly increased in the lateral septal nuclei of 1,25D treated mice in the early remyelination phase. Our results indicate that vitamin D may affect remyelination by mechanisms involving calcium signaling and mitochondrial function.
Disclosure:
Agnes Elisabeth Nystad: has received an unrestricted grant from Novartis.
Eystein Oveland: nothing to disclose.
Frode Berven: nothing to disclose.
Kjell-Morten Myhr has served on scientific advisory boards for Novartis Norway, Biogen Idec, Genzyme and Roche; received speaker honoraria from Genzyme, Sanofi-Aventis, Novartis, Biogen Idec and Teva and received unrestricted research support from, Sanofi-Aventis, Novartis, Biogen Idec, and the Norwegian MS Society.
Øivind Torkildsen has served on scientific advisory boards for Genzyme, Merck-Serono and Biogen Idec and received speaker honoraria and travel grants from Genzyme, Merck-Serono, Novartis, and Biogen-Idec.
Stig Wergeland has received speaker honoraria, unrestricted research support and travel grants from Biogen Idec and Novartis and travel grant from Merck.
This work was funded by the Kristian Gerhard Jebsen Foundation and unrestricted grants from Novartis.