Thrombin regulates the ability of Schwann cells to support neuritogenesis and to maintain the integrity of the nodes of Ranvier
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,...
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| Format: | Article |
| Language: | English |
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PAGEPress Publications
2020-03-01
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| Series: | European Journal of Histochemistry |
| Subjects: | |
| Online Access: | https://www.ejh.it/index.php/ejh/article/view/3109 |
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| author | Elena Pompili Viviana Ciraci Stefano Leone Valerio De Franchis Pietro Familiari Roberto Matassa Giuseppe Familiari Ada Maria Tata Lorenzo Fumagalli Cinzia Fabrizi |
| author_facet | Elena Pompili Viviana Ciraci Stefano Leone Valerio De Franchis Pietro Familiari Roberto Matassa Giuseppe Familiari Ada Maria Tata Lorenzo Fumagalli Cinzia Fabrizi |
| author_sort | Elena Pompili |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T14:25:14Z |
| format | Article |
| id | doaj.art-6977bd8aab064df49739eb9d7cd18497 |
| institution | Directory Open Access Journal |
| issn | 1121-760X 2038-8306 |
| language | English |
| last_indexed | 2024-04-12T14:25:14Z |
| publishDate | 2020-03-01 |
| publisher | PAGEPress Publications |
| record_format | Article |
| series | European Journal of Histochemistry |
| spelling | doaj.art-6977bd8aab064df49739eb9d7cd184972022-12-22T03:29:28ZengPAGEPress PublicationsEuropean Journal of Histochemistry1121-760X2038-83062020-03-0164210.4081/ejh.2020.3109Thrombin regulates the ability of Schwann cells to support neuritogenesis and to maintain the integrity of the nodes of RanvierElena Pompili0Viviana Ciraci1Stefano Leone2Valerio De Franchis3Pietro Familiari4Roberto Matassa5Giuseppe Familiari6Ada Maria Tata7Lorenzo Fumagalli8Cinzia Fabrizi9Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of RomeInstitute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of LisboaDepartment of Biology, Roma Tre University, RomeDepartment of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of RomeDepartment of Neuroscience, Mental Health and Sense Organs NESMOS, Sapienza University of RomeDepartment of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of RomeDepartment of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of RomeDepartment of Biology and Biotechnology Charles Darwin;Research Center in Neurobiology, Sapienza University of RomeDepartment of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of RomeDepartment of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of RomeSchwann 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.https://www.ejh.it/index.php/ejh/article/view/3109Protease-activated receptor 1gliaratperipheral nervous system |
| spellingShingle | Elena Pompili Viviana Ciraci Stefano Leone Valerio De Franchis Pietro Familiari Roberto Matassa Giuseppe Familiari Ada Maria Tata Lorenzo Fumagalli Cinzia Fabrizi Thrombin regulates the ability of Schwann cells to support neuritogenesis and to maintain the integrity of the nodes of Ranvier European Journal of Histochemistry Protease-activated receptor 1 glia rat peripheral nervous system |
| title | Thrombin regulates the ability of Schwann cells to support neuritogenesis and to maintain the integrity of the nodes of Ranvier |
| title_full | Thrombin regulates the ability of Schwann cells to support neuritogenesis and to maintain the integrity of the nodes of Ranvier |
| title_fullStr | Thrombin regulates the ability of Schwann cells to support neuritogenesis and to maintain the integrity of the nodes of Ranvier |
| title_full_unstemmed | Thrombin regulates the ability of Schwann cells to support neuritogenesis and to maintain the integrity of the nodes of Ranvier |
| title_short | Thrombin regulates the ability of Schwann cells to support neuritogenesis and to maintain the integrity of the nodes of Ranvier |
| title_sort | thrombin regulates the ability of schwann cells to support neuritogenesis and to maintain the integrity of the nodes of ranvier |
| topic | Protease-activated receptor 1 glia rat peripheral nervous system |
| url | https://www.ejh.it/index.php/ejh/article/view/3109 |
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