title: ST8SIA2 promotes oligodendrocyte differentiation and the integrity of myelin and axons.
abstract: ST8SIA2 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;65:34-49.
authors.affiliation: Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, ul. Ks. Trojdena 4, Warszawa, 02-109, Poland.|Laboratory of Molecular Neurobiology, Centre of New Technologies, University of Warsaw, ul. Banacha 2C, Warszawa, 02-097, Poland.|Postgraduate School of Molecular Medicine, ul. Zwirki i Wigury 61, Warszawa, 02-091, Poland.
authors.forename: Lukasz Mateusz
authors.initials: LM
authors.lastname: Szewczyk
authors.affiliation: Laboratory of Molecular Neurobiology, Centre of New Technologies, University of Warsaw, ul. Banacha 2C, Warszawa, 02-097, Poland.|Postgraduate School of Molecular Medicine, ul. Zwirki i Wigury 61, Warszawa, 02-091, Poland.
authors.forename: Nikola
authors.initials: N
authors.lastname: Brozko
authors.affiliation: Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, ul. Ks. Trojdena 4, Warszawa, 02-109, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Nagalski
authors.affiliation: Institute for Cellular Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, 30625, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Röckle
authors.affiliation: Institute for Cellular Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, 30625, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Werneburg
authors.affiliation: Institute for Cellular Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, 30625, Germany.
authors.forename: Herbert
authors.identifier: 0000-0002-1044-0881
authors.initials: H
authors.lastname: Hildebrandt
authors.affiliation: Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, ul. Ks. Trojdena 4, Warszawa, 02-109, Poland.|Laboratory of Molecular Neurobiology, Centre of New Technologies, University of Warsaw, ul. Banacha 2C, Warszawa, 02-097, Poland.
authors.forename: Marta Barbara
authors.initials: MB
authors.lastname: Wisniewska
authors.affiliation: Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, ul. Ks. Trojdena 4, Warszawa, 02-109, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Kuznicki
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012799:Sialyltransferases / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; C046778:CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase; D012799:Sialyltransferases
keywords: Schizophrenia; St8sia2; myelin; oligodendrocyte; polysialic acid