RESUMO
We have previously demonstrated that Sox17 expression is prominent at developmental stages corresponding to oligodendrocyte progenitor cell (OPC) cycle exit and onset of differentiation, and that Sox17 promotes initiation of OPC differentiation. In this study, we examined Sox17 expression and regulation under pathological conditions, particularly in two animal models of demyelination/remyelination and in post-mortem multiple sclerosis (MS) brain lesions. We found that the number of Sox17 expressing cells was significantly increased in lysolecithin (LPC)-induced lesions of the mouse spinal cord between 7 and 30 days post-injection, as compared with controls. Sox17 immunoreactivity was predominantly detected in Olig2(+) and CC1(+) oligodendrocytes and rarely in NG2(+) OPCs. The highest density of Sox17(+) oligodendrocytes was observed at 2 weeks after LPC injection, coinciding with OPC differentiation. Consistent with these findings, in cuprizone-treated mice, Sox17 expression was highest in newly generated and in maturing CC1(+) oligodendrocytes, but low in NG2(+) OPCs during the demyelination and remyelination phases. In MS tissue, Sox17 was primarily detected in actively demyelinating lesions and periplaque white matter. Sox17 immunoreactivity was co-localized with NOGO-A+ post-mitotic oligodendrocytes both in active MS lesions and periplaque white matter. Taken together, our data: (i) demonstrate that Sox17 expression is highest in newly generated oligodendrocytes under pathological conditions and could be used as a marker of oligodendrocyte regeneration, and (ii) are suggestive of Sox17 playing a critical role in oligodendrocyte differentiation and lesion repair.
Assuntos
Encéfalo/patologia , Doenças Desmielinizantes/patologia , Esclerose Múltipla/patologia , Oligodendroglia/metabolismo , Fatores de Transcrição SOXF/metabolismo , Idoso , Animais , Antígenos/metabolismo , Proteínas Relacionadas à Autofagia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Bromodesoxiuridina/metabolismo , Cuprizona/toxicidade , Doenças Desmielinizantes/induzido quimicamente , Modelos Animais de Doenças , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Inibidores da Monoaminoxidase/toxicidade , Proteína Básica da Mielina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fator de Transcrição 2 de Oligodendrócitos , Proteoglicanas/metabolismo , Fatores de Tempo , Regulação para Cima/efeitos dos fármacosRESUMO
Objetivo: Caracterizar la expresión y función de alphaB cristalina en la lesión medular. Material y método: En un modelo animal murino -mus musculus (ratón) de la cepa C57/Bl6- se realizó lesión medular mediante contusión, y los segmentos medulares fueron extraídos a los 1, 3, 7, 14, 21 y 28 días postlesión. Se valoraron los niveles de ARNm de alpaB cristalina. Asimismo, se administró alphaB cristalina recombinante humana tras la lesión medular y se valoró su efecto sobre la recuperación funcional. Resultados: Los niveles de expresión de alphaB cristalina no se incrementan hasta los 21 días post-lesión. La administración de dicha proteína promueve recuperación funcional tras la lesión medular. Conclusión: La administración de alphaB cristalina podría ser una nueva terapia para tratar las lesiones agudas de la médula espinal (AU)
Objective: Characterize the expression and role of alphaB crystallin in spinal cord injury Material and method: In a murine animal model (mus musculus (C57/Bl6 mouse) spinal cord injury was induced by contusion and the spinal cord segment corresponding to the injury site was extracted at day 1, 3, 7, 14, 21, 28 post-injury and alphaB crystallin mRNA levels were assessed. In addition, the effects of the administration of the human alphaB crystallin recombinant protein after spinal cord injury was evaluated. Results: alphaB crystallin mRNA levels did not increase until day 21 following spinal cord injury. Administration of alphaB crystallin resulted in increased functional recovery after lesion. Conclusion: Administration of alphaB crystallin could therefore be valuable for the treatment of acute spinal cord injury (AU)