Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6017203 | Experimental Neurology | 2015 | 11 Pages |
Abstract
Successful regeneration of injured peripheral nerves is mainly attributed to the plastic behavior of Schwann cells. Upon loss of axons, these cells trans-differentiate into regeneration promoting repair cells which provide trophic support to regrowing axons. Among others, activation of cJun was revealed to be involved in this process, initiating the stereotypic pattern of Schwann cell phenotype alterations during Wallerian degeneration. Nevertheless, the ability of Schwann cells to adapt and therefore the nerve's potential to regenerate can be limited in particular after long term denervation or in neuropathies leading to incomplete regeneration only and thus emphasizing the need for novel therapeutic approaches. Here we stimulated primary neonatal and adult rat Schwann cells with Fingolimod/FTY720P and investigated its impact on the regeneration promoting phenotype. FTY720P activated a number of de-differentiation markers including cJun and interfered with maturation marker and myelin expression. Functionally, FTY720P treated Schwann cells upregulated growth factor expression and these cells enhanced dorsal root ganglion neurite outgrowth on inhibitory substrates. Our results therefore provide strong evidence that FTY720P application supports the generation of a repair promoting cellular phenotype and suggest that Fingolimod could be used as treatment for peripheral nerve injuries and diseases.
Keywords
GDNFODCcJunGBSOPCOrnithine decarboxylaseEAEPMP22platelet derived growth factor-BBNeuregulin-1MAGp38MAPKGPR37S1PRSox2CIDPp75NTRNRG1EANGap43MALperiaxinPDGF-BBDRGoligodendrocyte transcription factor 1SRY (sex determining region Y)-Box 2MBPGAPDHOlig1TGFβKrox20Myelin and lymphocyte proteinCx32ERKPRXTYRP1Oct-6BDNFcAMPDMSOIgf1experimental autoimmune neuritisPKB, Protein kinase BCyclic adenosine monophosphateexperimental autoimmune encephalomyelitisAktPeripheral nerve regenerationtransforming growth factor-betaTrans-differentiationCNSDimethyl sulfoxideAxon outgrowthgrowth associated protein 43central nervous systemperipheral nervous systemextracellular-signal regulated kinasefigureFigbrain derived neurotrophic factorinsulin-like growth factor 1Glial cell line derived neurotrophic factorphosphatase and tensin homologChronic inflammatory demyelinating polyneuropathyMyelinNeuropathyprotein zerotyrosinase-related protein 1Myelin basic proteinp38 mitogen-activated protein kinasePeripheral myelin protein 22PtenPNSConnexin-32dorsal root gangliaglyceraldehyde 3-phosphate dehydrogenaseMyelin associated glycoproteinsphingosine-1-phosphate receptorp75 neurotrophin receptorGlia
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Authors
André Heinen, Felix Beyer, Nevena Tzekova, Hans-Peter Hartung, Patrick Küry,