Publicação
Role of S100B on central nervous system demyelination and remyelination
| Resumo: | S100B is a small Ca2+ binding protein member of S100 family. Within the central nervous system, S100B is mostly expressed by astrocytes, though it has been shown to be also expressed by oligodendrocytes, microglia and some neural populations. S100B exerts both intracellular and extracellular functions. Within cells S100B acts as a signaling molecule, being involved in the regulation of energy metabolism and in the modulation of both proliferation and differentiation of neurons and glia. When secreted to the extracellular space, S100B exerts beneficial or detrimental effects in a concentration-dependent manner: (i) nanomolar concentrations have been reported to exert trophic effects whereas (ii) micromolar concentrations have shown to produce neurodegenerative, neuroinflammatory and/or apoptotic outcomes. Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease with a neurodegenerative component, characterized by the occurrence of focal areas of inflammatory demyelination, variable gliosis and relative axonal loss, with limited remyelination. Moreover, data from previous research of other authors and from ongoing work of our group have shown augmented S100B in both CSF, serum and post-mortem plaques of MS patients. With this work we intended to explore the role of S100B in MS main mechanisms. For this end we used mouse cerebellar organotypic slice cultures, a previously described model of demyelination. Therefore, we first evaluated the expression and secretion of S100B in the course of a demyelinating insult. Our results reveal that S100B is released and overexpressed upon demyelination mainly by astrocytes. Next, we also evaluated in what way S100B might affect demyelination, reactivity of glial cells and inflammatory response in consequence of demyelination, by blocking extracellular S100B with a specific antibody. Upon the demyelination insult, we verified an upregulation of myelin proteins and pro-inflammatory cytokines gene expression, as well as activation of astrocytes and microglia. In turn, blockade of S100B appeared to prevent demyelination and reduce both reactive gliosis and expression of pro-inflammatory factors. Altogether, these data strongly suggest that high levels of S100B may exacerbate demyelination and/or delay remyelination. |
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| Autores principais: | Afonso, Vera Alexandra Padrela Martins |
| Assunto: | S100B Multiple Sclerosis Demyelination Inflammatory response Teses de mestrado - 2014 |
| Ano: | 2014 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | S100B is a small Ca2+ binding protein member of S100 family. Within the central nervous system, S100B is mostly expressed by astrocytes, though it has been shown to be also expressed by oligodendrocytes, microglia and some neural populations. S100B exerts both intracellular and extracellular functions. Within cells S100B acts as a signaling molecule, being involved in the regulation of energy metabolism and in the modulation of both proliferation and differentiation of neurons and glia. When secreted to the extracellular space, S100B exerts beneficial or detrimental effects in a concentration-dependent manner: (i) nanomolar concentrations have been reported to exert trophic effects whereas (ii) micromolar concentrations have shown to produce neurodegenerative, neuroinflammatory and/or apoptotic outcomes. Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease with a neurodegenerative component, characterized by the occurrence of focal areas of inflammatory demyelination, variable gliosis and relative axonal loss, with limited remyelination. Moreover, data from previous research of other authors and from ongoing work of our group have shown augmented S100B in both CSF, serum and post-mortem plaques of MS patients. With this work we intended to explore the role of S100B in MS main mechanisms. For this end we used mouse cerebellar organotypic slice cultures, a previously described model of demyelination. Therefore, we first evaluated the expression and secretion of S100B in the course of a demyelinating insult. Our results reveal that S100B is released and overexpressed upon demyelination mainly by astrocytes. Next, we also evaluated in what way S100B might affect demyelination, reactivity of glial cells and inflammatory response in consequence of demyelination, by blocking extracellular S100B with a specific antibody. Upon the demyelination insult, we verified an upregulation of myelin proteins and pro-inflammatory cytokines gene expression, as well as activation of astrocytes and microglia. In turn, blockade of S100B appeared to prevent demyelination and reduce both reactive gliosis and expression of pro-inflammatory factors. Altogether, these data strongly suggest that high levels of S100B may exacerbate demyelination and/or delay remyelination. |
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