Thrombin regulates the ability of Schwann cells to support neuritogenesis and to maintain the integrity of the nodes of Ranvier

Abstract

Schwann cells (SC) are characterized by a remarkable plasticity that enables them to promptly respond to nerve injury promoting axonal regeneration. In peripheral nerves after damage SC convert to a repair-promoting phenotype activating a sequence of supportive functions that drive myelin clearance, prevent neuronal death, and help axon growth and guidance. Regeneration of peripheral nerves after damage correlates inversely with thrombin levels. Thrombin is not only the key regulator of the coagulation cascade but also a protease with hormone-like activities that affects various cells of the central and peripheral nervous system mainly through the protease-activated receptor 1 (PAR1). Aim of the present study was to investigate if and how thrombin could affect the axon supportive functions of SC. In particular, our results show that the activation of PAR1 in rat SC cultures with low levels of thrombin or PAR1 agonist peptides induces the release of molecules, which favor neuronal survival and neurite elongation. Conversely, the stimulation of SC with high levels of thrombin or PAR1 agonist peptides drives an opposite effect inducing SC to release factors that inhibit the extension of neurites. Moreover, high levels of thrombin administered to sciatic nerve ex vivo explants induce a dramatic change in SC morphology causing disappearance of the Cajal bands, enlargement of the Schmidt-Lanterman incisures and calcium-mediated demyelination of the paranodes. Our results indicate thrombin as a novel modulator of SC plasticity potentially able to favor or inhibit SC pro-regenerative properties according to its level at the site of lesion.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.
Published
2020-03-30
Info
Issue
Section
Articles
Supporting Agencies
This work was supported by grants from Sapienza University to CF (RM118164328DF7F2 and RM11916B88BF39BB)
Keywords:
Protease-activated receptor 1, glia, rat, peripheral nervous system
Statistics
  • Abstract views: 257

  • PDF: 112
  • HTML: 2
How to Cite
Pompili, E., Ciraci, V., Leone, S., De Franchis, V., Familiari, P., Matassa, R., Familiari, G., Tata, A. M., Fumagalli, L., & Fabrizi, C. (2020). Thrombin regulates the ability of Schwann cells to support neuritogenesis and to maintain the integrity of the nodes of Ranvier. European Journal of Histochemistry, 64(2). https://doi.org/10.4081/ejh.2020.3109