Contributions
Abstract: P435
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models
Cuprizone (CPZ) induced demyelination and oligodendrocyte loss share molecular pathways with those observed in brain lesions of patients with multiple sclerosis (MS), and differentially expression of microRNAs in MS lesions has been described.
We examined microRNA expression in the corpus callosum of mice during CPZ-induced de- and remyelination. Agilent Mouse miRNA Microarray and quantitative PCR showed differential expression of miR-146a, miR-181b and miR-193a. By using miR-146a deficient (KO) mice, we found that absence of miR-146a protected against demyelination, axonal loss, weight loss and atrophy of thymus and spleen.
A proteome dataset obtained during CPZ induced de- and remyelination in the WT mice indicated that protein levels of miR-146a target genes, SNAP25 and SMAD4 were decreased during demyelination. By comparing the expression of SNAP25 and SMAD4 between miR-146a KO mice and WT mice by ELISA, we observed higher levels of SNAP25 in the miR-146a KO mice, but there was no difference between KO and WT mice during demyelination. Meso Scale Discovery multiplex analysis of the corpus callosum revealed upregulated TNF-R1, TNF-RII and CCL2 proteins in the wild-type (WT) mice, but not in the miR-146a KO mice during demyelination, and TNF-RII and CCL2 levels were lower in the KO mice in the demyelination phase.
Our data indicate that absence of miR-146a alters inflammatory responses in the corpus callosum and protects against demyelination and axonal loss.
Disclosure: Supported by Lundbeckfonden R118-A11472, OTKA-NN109841, OTKA-K77892, Region of Southern Denmark 14/24200, Jascha Fonden 5589, Direktør Ejnar Jonasson kaldet Johnsen og hustrus mindelegat 5609, Odense University Hospital (OUH) A474, Fonden for Lægevidenskabensfremme 13-267. We thank Ulla Damgaard Munk and Helle Vinsløv Jensen for expert technical assistance.
Zsolt Illes has served on scientific advisory boards, served as a consultant, received support for congress participation, received speaker honoraria, and received research support from Biogen, Merck-Serono, Sanofi-Genzyme, Lundbeck, and Novartis.
Abstract: P435
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models
Cuprizone (CPZ) induced demyelination and oligodendrocyte loss share molecular pathways with those observed in brain lesions of patients with multiple sclerosis (MS), and differentially expression of microRNAs in MS lesions has been described.
We examined microRNA expression in the corpus callosum of mice during CPZ-induced de- and remyelination. Agilent Mouse miRNA Microarray and quantitative PCR showed differential expression of miR-146a, miR-181b and miR-193a. By using miR-146a deficient (KO) mice, we found that absence of miR-146a protected against demyelination, axonal loss, weight loss and atrophy of thymus and spleen.
A proteome dataset obtained during CPZ induced de- and remyelination in the WT mice indicated that protein levels of miR-146a target genes, SNAP25 and SMAD4 were decreased during demyelination. By comparing the expression of SNAP25 and SMAD4 between miR-146a KO mice and WT mice by ELISA, we observed higher levels of SNAP25 in the miR-146a KO mice, but there was no difference between KO and WT mice during demyelination. Meso Scale Discovery multiplex analysis of the corpus callosum revealed upregulated TNF-R1, TNF-RII and CCL2 proteins in the wild-type (WT) mice, but not in the miR-146a KO mice during demyelination, and TNF-RII and CCL2 levels were lower in the KO mice in the demyelination phase.
Our data indicate that absence of miR-146a alters inflammatory responses in the corpus callosum and protects against demyelination and axonal loss.
Disclosure: Supported by Lundbeckfonden R118-A11472, OTKA-NN109841, OTKA-K77892, Region of Southern Denmark 14/24200, Jascha Fonden 5589, Direktør Ejnar Jonasson kaldet Johnsen og hustrus mindelegat 5609, Odense University Hospital (OUH) A474, Fonden for Lægevidenskabensfremme 13-267. We thank Ulla Damgaard Munk and Helle Vinsløv Jensen for expert technical assistance.
Zsolt Illes has served on scientific advisory boards, served as a consultant, received support for congress participation, received speaker honoraria, and received research support from Biogen, Merck-Serono, Sanofi-Genzyme, Lundbeck, and Novartis.