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ST8SIA2 promotes oligodendrocyte differentiation and the integrity of myelin and axons

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cris.lastimport.scopus2024-02-12T19:53:10Z
dc.abstract.enST8SIA2 is a polysialyltransferase that attaches polysialic acid to the glycoproteins NCAM1 and CADM1. Polysialylation is involved in brain development and plasticity. ST8SIA2 is a schizophrenia candidate gene, and St8sia2−/− mice exhibit schizophrenia-like behavior. We sought to identify new pathological consequences of ST8SIA2 deficiency. Our proteomic analysis suggested myelin impairment in St8sia2−/− mice. Histological and immune staining together with Western blot revealed that the onset of myelination was not delayed in St8sia2−/− mice, but the content of myelin was lower. Ultrastructure analysis of the corpus callosum showed thinner myelin sheaths, smaller and irregularly shaped axons, and white matter lesions in adult St8sia2−/− mice. Then we evaluated oligodendrocyte differentiation in vivo and in vitro. Fewer OLIG2+ cells in the cortex and corpus callosum, together with the higher percentage of undifferentiated oligodenroglia in St8sia2−/− mice suggested an impairment in oligodendrocyte generation. Experiment on primary cultures of oligodendrocyte precursor cells (OPCs) confirmed a cell-autonomous effect of ST8SIA2 in oligodendroglia, and demonstrated that OPC to oligodendrocyte transition is inhibited in St8sia2−/− mice. Concluding, ST8SIA2-mediated polysialylation influences on oligodendrocyte differentiation, and oligodendrocyte deficits in St8sia2 mice are a possible cause of the demyelination and degeneration of axons, resembling nerve fiber alterations in schizophrenia. GLIA 2016
dc.affiliationUniwersytet Warszawski
dc.contributor.authorKuźnicki, Jacek
dc.contributor.authorHildebrandt, Herbert
dc.contributor.authorWiśniewska, Marta
dc.contributor.authorWerneburg, Sebastian
dc.contributor.authorRöckle, Iris
dc.contributor.authorSzewczyk, Łukasz
dc.contributor.authorNagalski, Andrzej
dc.date.accessioned2024-01-26T08:07:29Z
dc.date.available2024-01-26T08:07:29Z
dc.date.copyright2016-08-18
dc.date.issued2017
dc.description.accesstimeBEFORE_PUBLICATION
dc.description.financeNie dotyczy
dc.description.number1
dc.description.versionFINAL_PUBLISHED
dc.description.volume65
dc.identifier.doi10.1002/GLIA.23048
dc.identifier.issn0894-1491
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/120541
dc.identifier.weblinkhttps://onlinelibrary.wiley.com/doi/full/10.1002/glia.23048
dc.languageeng
dc.pbn.affiliationbiological sciences
dc.relation.ispartofGLIA
dc.relation.pages34-49
dc.rightsCC-BY-NC-ND
dc.sciencecloudnosend
dc.subject.enSchizophrenia St8sia2 polysialic acid myelin oligodendrocyte
dc.titleST8SIA2 promotes oligodendrocyte differentiation and the integrity of myelin and axons
dc.typeJournalArticle
dspace.entity.typePublication