Contributions
Abstract: P463
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Introduction: Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system (CNS), characterized by focal areas of inflammation in which myelin, oligodendrocytes (OLGs) and neurons are damaged. Oncostatin M (OSM), a member of the interleukin (IL)-6 cytokine family, is produced in lesions of MS patients and we demonstrated in previous research that OSM protects against demyelination in the cuprizone mouse model and enhances neurite outgrowth during spinal cord injury.
Objectives: In this study, we investigate the role of OSM in remyelination in the cuprizone model, and its underlying mechanism.
Methods: Using cuprizone-induced demyelination in mice, we investigated the effect of OSM receptor deficiency in OSMR KO mice on one hand and the effect of local OSM overexpression (using stereotactical injection of lentiviral vectors) on the other hand. Tissue analysis by means of qPCR and immunohistochemistry was done to reveal differences in genotypes or treatment groups. In vitro cell cultures were used to determine mechanistic processes.
Results: Here, we show that OSMR-deficient mice have an impaired remyelinative capacity after cuprizone-induced demyelination. In parallel, local OSM overexpression enhanced remyelination. Interestingly, we found that local OSM overexpression induced activation of astrocytes, and that these astrocytes produced TIMP-1, a matrix metalloproteinase inhibitor. To assess whether TIMP-1 is the downstream mediator of OSM in enhancing remyelination, TIMP-1 KO mice were fed a cuprizone diet. TIMP-1 KO mice phenocopied OSMR KO mice and showed reduced remyelination. Currently, the mechanism of TIMP-1 mediated remyelination is being investigated.
Conclusions: Local expression of OSM in demyelinated lesions activates astrocytes to produce TIMP-1, which enables remyelination. Exploring this further will result in important fundamental and therapeutically applicable knowledge for MS patients.
Disclosure: Evelien Houben: nothing to disclose. Kris Janssens: nothing to disclose. Ivo Lambrichts: nothing to disclose. Veerle Baekelandt: nothing to disclose. Melissa Schepers: nothing to disclose. Tim Vanmierlo: nothing to disclose. Helena Slaets: nothing to disclose. Bieke Broux: nothing to disclose. Niels Hellings: nothing to disclose.
Abstract: P463
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Introduction: Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system (CNS), characterized by focal areas of inflammation in which myelin, oligodendrocytes (OLGs) and neurons are damaged. Oncostatin M (OSM), a member of the interleukin (IL)-6 cytokine family, is produced in lesions of MS patients and we demonstrated in previous research that OSM protects against demyelination in the cuprizone mouse model and enhances neurite outgrowth during spinal cord injury.
Objectives: In this study, we investigate the role of OSM in remyelination in the cuprizone model, and its underlying mechanism.
Methods: Using cuprizone-induced demyelination in mice, we investigated the effect of OSM receptor deficiency in OSMR KO mice on one hand and the effect of local OSM overexpression (using stereotactical injection of lentiviral vectors) on the other hand. Tissue analysis by means of qPCR and immunohistochemistry was done to reveal differences in genotypes or treatment groups. In vitro cell cultures were used to determine mechanistic processes.
Results: Here, we show that OSMR-deficient mice have an impaired remyelinative capacity after cuprizone-induced demyelination. In parallel, local OSM overexpression enhanced remyelination. Interestingly, we found that local OSM overexpression induced activation of astrocytes, and that these astrocytes produced TIMP-1, a matrix metalloproteinase inhibitor. To assess whether TIMP-1 is the downstream mediator of OSM in enhancing remyelination, TIMP-1 KO mice were fed a cuprizone diet. TIMP-1 KO mice phenocopied OSMR KO mice and showed reduced remyelination. Currently, the mechanism of TIMP-1 mediated remyelination is being investigated.
Conclusions: Local expression of OSM in demyelinated lesions activates astrocytes to produce TIMP-1, which enables remyelination. Exploring this further will result in important fundamental and therapeutically applicable knowledge for MS patients.
Disclosure: Evelien Houben: nothing to disclose. Kris Janssens: nothing to disclose. Ivo Lambrichts: nothing to disclose. Veerle Baekelandt: nothing to disclose. Melissa Schepers: nothing to disclose. Tim Vanmierlo: nothing to disclose. Helena Slaets: nothing to disclose. Bieke Broux: nothing to disclose. Niels Hellings: nothing to disclose.