ST8SIA2 gene deficiency leads to aged-related axonal degeneration and weakening of myelin sheath

• Autorzy: Szewczyk L. , Brozko N. , Nagalski A. , Liszewska E. , Zawadzka M. , Hildebrandt H. , Kuznicki J. , Wisniewska M.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: This study was to investigate the involvement of ST8SIA2 in myelination of the brain. ST8SIA2 and its paralog ST8SIA4 synthesize polysialic acid chains (PSA) to NCAMs. Synthesis of PSA and its downregulation during brain development are crucial for a proper myelin formation. However, myelin forms normally in St8sia4-/- mice. So far, myelin-related phenotype of St8sia2-/- mice has not been investigated. METHODS: Mass-spectrometry, westernblot, myelin staining, immunostaining, electron microscopy RESULTS: Quantitative mass-spectrometry showed that the levels of myelin proteins MBP and PLP1 in the hippocampus are lower in adult St8sia2-/- mice than in control. Westernblot confirmed this result and revealed the same changes in cortical areas. Then, in order to determine the onset of the myelin impairment in the knockout mice, we labeled white matter in brain sections from mice at postnatal ages (P15 to P240) with Black Gold II, and showed that this phenotype develops with age. In agreement with this result, western blot analysis of major myelin proteins: PLP1, MBP, MOBP, MOG and CNPase, in the brain of mice from P15 to P90 revealed their lower levels in the knockouts, especially in the older mice. Electron microscopy revealed thinning of myelin sheath in the adult knockouts at P90 and P240, as well as abnormalities in axonal morphology and their degeneration at P240. Western blot revealed twofold lower levels of neurofilament proteins also suggesting axonopathy. CONCLUSIONS: ST8SIAII-mediated deficiency of polysialylation leads to axonal pathologies and their degeneration accompanied by myelin weakening. A decrease in polysialylated NCAM has been observed in postmortem schizophrenics brains, and the mice lacking the St8sia2 gene display schizophrenia-related behavior and anatomical abnormalities. We propose that myelin and axonal pathologies of schizophrenics might be a consequence of unsufficient level of polysialylation during development and in early adulthood.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S69

Twórcy

autor

Szewczyk L.

• International Institute of Molecular and Cell Biology, Warsaw, Poland
• Center of New Technologies, University of Warsaw, Warsaw, Poland

autor

Brozko N.

• Center of New Technologies, University of Warsaw, Warsaw, Poland;

autor

Nagalski A.

• International Institute of Molecular and Cell Biology, Warsaw, Poland

autor

Liszewska E.

• Nencki Insitute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Zawadzka M.

• Nencki Insitute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Hildebrandt H.

• Hannover Medical School, Hannover, Germany

autor

Kuznicki J.

• International Institute of Molecular and Cell Biology, Warsaw, Poland

autor

Wisniewska M.

• International Institute of Molecular and Cell Biology, Warsaw, Poland
• Center of New Technologies, University of Warsaw, Warsaw, Poland