Aarhus Universitet

Christian Bjerggaard Vægter

Peripheral Nerve Regeneration Is Independent From Schwann Cell p75NTR Expression

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DOI

  • Nádia P Gonçalves
  • Simin Mohseni, Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
  • ,
  • Marwa El Soury, Department of Clinical and Biological Sciences, University of Turin, Orbassano, TO, Italy; Neuroscience Institute of the "Cavalieri Ottolenghi" Foundation (NICO), University of Turin, Orbassano, TO, Italy.
  • ,
  • Maj Ulrichsen
  • Mette Richner
  • Junhua Xiao, Department of Anatomy and Neuroscience, School of Biomedical Science, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia.
  • ,
  • Rhiannon J Wood, Department of Anatomy and Neuroscience, School of Biomedical Science, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia.
  • ,
  • Olav M Andersen
  • Elizabeth J Coulson, School of Biomedical Sciences, Faculty of Medicine, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
  • ,
  • Stefania Raimondo, Department of Anatomy and Neuroscience, School of Biomedical Science, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia.
  • ,
  • Simon S Murray, Department of Anatomy and Neuroscience, School of Biomedical Science, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia.
  • ,
  • Christian B Vægter

Schwann cell reprogramming and differentiation are crucial prerequisites for neuronal regeneration and re-myelination to occur following injury to peripheral nerves. The neurotrophin receptor p75NTR has been identified as a positive modulator for Schwann cell myelination during development and implicated in promoting nerve regeneration after injury. However, most studies base this conclusion on results obtained from complete p75NTR knockout mouse models and cannot dissect the specific role of p75NTR expressed by Schwann cells. In this present study, a conditional knockout model selectively deleting p75NTR expression in Schwann cells was generated, where p75NTR expression is replaced with that of an mCherry reporter. Silencing of Schwann cell p75NTR expression was confirmed in the sciatic nerve in vivo and in vitro, without altering axonal expression of p75NTR. No difference in sciatic nerve myelination during development or following sciatic nerve crush injury was observed, as determined by quantification of both myelinated and unmyelinated nerve fiber densities, myelinated axonal diameter and myelin thickness. However, the absence of Schwann cell p75NTR reduced motor nerve conduction velocity after crush injury. Our data indicate that the absence of Schwann cell p75NTR expression in vivo is not critical for axonal regrowth or remyelination following sciatic nerve crush injury, but does play a key role in functional recovery. Overall, this represents the first step in redefining the role of p75NTR in the peripheral nervous system, suggesting that the Schwann cell-axon unit functions as a syncytium, with the previous published involvement of p75NTR in remyelination most likely depending on axonal/neuronal p75NTR and/or mutual glial-axonal interactions.

OriginalsprogEngelsk
Artikelnummer235
TidsskriftFrontiers in Cellular Neuroscience
Vol/bind13
Antal sider14
ISSN1662-5102
DOI
StatusUdgivet - 2019

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