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Journal of Neural Transmission

, Volume 122, Issue 9, pp 1211–1219 | Cite as

In vivo stimulation of early peripheral axon regeneration by N-propionylmannosamine in the presence of polysialyltransferase ST8SIA2

  • Georgios KoulaxouzidisEmail author
  • Werner Reutter
  • Herbert Hildebrandt
  • G. Björn Stark
  • Christian Witzel
Translational Neurosciences - Original Article

Abstract

The key enzyme of sialic acid (Sia) biosynthesis is the bifunctional UDP-N-acetylglucosamine 2-epimerase/ManNAc kinase (GNE/MNK). It metabolizes the physiological precursor ManNAc and N-acyl modified analogues such as N-propionylmannosamine (ManNProp) to the respective modified sialic acid. Polysialic acid (polySia) is a crucial compound for several functions in the nervous system and is synthesized by the polysialyltransferases ST8SIA2 and ST8SIA4. PolySia can be modified in vitro and in vivo by metabolic glycoengineering of the N-acyl side chain of Sia. In vitro studies show that the application of ManNProp increases neurite outgrowth and accelerates the re-establishment of functional synapses. In this study, we investigate in vivo how ManNProp application might benefit peripheral nerve regeneration. In mice expressing axonal fluorescent proteins (thy-1-YFP), we transected the sciatic nerve and then replaced part of it with a sciatic nerve graft from non-expressing mice (wild-type mice or St8sia2 / mice). Analyses conducted 5 days after grafting showed that systemic application of ManNProp (200 mg/kg, twice a day, i.p.), but not of physiological ManNAc (1 g/kg, twice a day, i.p.), significantly increased the extent of axonal elongation, the number of arborizing axons and the number of branches per regenerating axon within the grafts from wild-type mice, but not in those from St8sia2 / mice. The results demonstrate that the application of ManNProp has beneficial effects on early peripheral nerve regeneration and indicate that the stimulation of axon growth depends on ST8SIA2 activity in the nerve graft.

Keywords

Polysialyltransferases Metabolic glycoengineering ManNProp Thy-1-YFP St8sia2/ mice 

Notes

Acknowledgments

This study received financial support from the Sonnenfeld Stiftung (Berlin, Germany), which played no part in designing the study or in collecting, analysing and interpreting the data.

Conflict of interest

The authors have no conflicts of interest to declare.

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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Georgios Koulaxouzidis
    • 1
    Email author
  • Werner Reutter
    • 2
  • Herbert Hildebrandt
    • 3
  • G. Björn Stark
    • 1
  • Christian Witzel
    • 4
  1. 1.Klinik für Plastische und HandchirurgieUniversitätsklinikum FreiburgFreiburgGermany
  2. 2.Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie Charité-Universitätsmedizin (Freie Universität Berlin)Berlin-DahlemGermany
  3. 3.Zelluläre Chemie, Zentrum Biochemie, Medizinische Hochschule HannoverHannoverGermany
  4. 4.Plastische, Rekonstruktive und Ästhetische Chirurgie, Interdisziplinäres Brustzentrum, Charité-Universitätsmedizin BerlinBerlinGermany

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