title: Down-regulation of polysialic acid is required for efficient myelin formation.
abstract: Oligodendrocyte precursor cells modify the neural cell adhesion molecule (NCAM) by the attachment of polysialic acid (PSA). Upon further differentiation into mature myelinating oligodendrocytes, however, oligodendrocyte precursor cells down-regulate PSA synthesis. In order to address the question of whether this down-regulation is a necessary prerequisite for the myelination process, transgenic mice expressing the polysialyltransferase ST8SiaIV under the control of the proteolipid protein promoter were generated. In these mice, postnatal down-regulation of PSA in oligodendrocytes was abolished. Most NCAM-120, the characteristic NCAM isoform in oligodendrocytes, carried PSA in the transgenic mice at all stages of postnatal development. Polysialylated NCAM-120 partially co-localized with myelin basic protein and was present in purified myelin. The permanent expression of PSA-NCAM in oligodendrocytes led to a reduced myelin content in the forebrains of transgenic mice during the period of active myelination and in the adult animal. In situ hybridizations indicated a significant decrease in the number of mature oligodendrocytes in the forebrain. Thus, down-regulation of PSA during oligodendrocyte differentiation is a prerequisite for efficient myelination by mature oligodendrocytes. Furthermore, myelin of transgenic mice exhibited structural abnormalities like redundant myelin and axonal degeneration, indicating that the down-regulation of PSA is also necessary for myelin maintenance.
authors.affiliation: Institute of Physiological Chemistry and Institute of Anatomy, University of Bonn, D-53115 Bonn, Germany.
authors.forename: Simon Ngamli
authors.initials: SN
authors.lastname: Fewou
authors.forename: Hariharasubramanian
authors.initials: H
authors.lastname: Ramakrishnan
authors.forename: Heinrich
authors.initials: H
authors.lastname: Büssow
authors.forename: Volkmar
authors.initials: V
authors.lastname: Gieselmann
authors.forename: Matthias
authors.initials: M
authors.lastname: Eckhardt
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000201:enzymology* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D016548:Prosencephalon / Q000201:enzymology* / Q000254:growth & development / Q000473:pathology; D020033:Protein Isoforms / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics; D012794:Sialic Acids / Q000096:biosynthesis* / Q000235:genetics; D012799:Sialyltransferases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; C047516:Plp1 protein, mouse; D020033:Protein Isoforms; D012794:Sialic Acids; C021319:polysialic acid; D012799:Sialyltransferases