Please use this identifier to cite or link to this item: https://scidar.kg.ac.rs/handle/123456789/10750
Full metadata record
DC FieldValueLanguage
dc.rights.licenseBY-NC-ND-
dc.contributor.authorRodríguez-Jiménez F.-
dc.contributor.authorVilches A.-
dc.contributor.authorPerez Arago M.-
dc.contributor.authorClemente E.-
dc.contributor.authorRomán Parrilla, Raquel-
dc.contributor.authorLeal J.-
dc.contributor.authorCastro A.-
dc.contributor.authorFustero, Santos-
dc.contributor.authormoreno, Victoria-
dc.contributor.authorJendelova P.-
dc.contributor.authorStojkovic, Miodrag-
dc.contributor.authorErceg, Slaven-
dc.date.accessioned2021-04-20T16:34:13Z-
dc.date.available2021-04-20T16:34:13Z-
dc.date.issued2020-01-01-
dc.identifier.issn19337213-
dc.identifier.urihttps://scidar.kg.ac.rs/handle/123456789/10750-
dc.description.abstract© 2020, The Author(s). The inhibition of glycogen synthase kinase-3 (GSK-3) can induce neurogenesis, and the associated activation of Wnt/β-catenin signaling via GSK-3 inhibition may represent a means to promote motor function recovery following spinal cord injury (SCI) via increased astrocyte migration, reduced astrocyte apoptosis, and enhanced axonal growth. Herein, we assessed the effects of GSK-3 inhibition in vitro on the neurogenesis of ependymal stem/progenitor cells (epSPCs) resident in the mouse spinal cord and of human embryonic stem cell–derived neural progenitors (hESC-NPs) and human-induced pluripotent stem cell–derived neural progenitors (hiPSC-NPs) and in vivo on spinal cord tissue regeneration and motor activity after SCI. We report that the treatment of epSPCs and human pluripotent stem cell–derived neural progenitors (hPSC-NPs) with the GSK-3 inhibitor Ro3303544 activates β-catenin signaling and increases the expression of the bIII-tubulin neuronal marker; furthermore, the differentiation of Ro3303544-treated cells prompted an increase in the number of terminally differentiated neurons. Administration of a water-soluble, bioavailable form of this GSK-3 inhibitor (Ro3303544-Cl) in a severe SCI mouse model revealed the increased expression of bIII-tubulin in the injury epicenter. Treatment with Ro3303544-Cl increased survival of mature neuron types from the propriospinal tract (vGlut1, Parv) and raphe tract (5-HT), protein kinase C gamma–positive neurons, and GABAergic interneurons (GAD65/67) above the injury epicenter. Moreover, we observed higher numbers of newly born BrdU/DCX-positive neurons in Ro3303544-Cl–treated animal tissues, a reduced area delimited by astrocyte scar borders, and improved motor function. Based on this study, we believe that treating animals with epSPCs or hPSC-NPs in combination with Ro3303544-Cl deserves further investigation towards the development of a possible therapeutic strategy for SCI.-
dc.relation.ispartofNeurotherapeutics-
dc.rightsopenAccess-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/-
dc.titleActivation of Neurogenesis in Multipotent Stem Cells Cultured In Vitro and in the Spinal Cord Tissue After Severe Injury by Inhibition of Glycogen Synthase Kinase-3-
dc.typearticle-
dc.identifier.doi10.1007/s13311-020-00928-0-
dc.identifier.scopus85091781604-
Appears in Collections:Faculty of Medical Sciences, Kragujevac

Page views(s)

74

Downloads(s)

5

Files in This Item:
File Description SizeFormat 
10.1007-s13311-020-00928-0.pdf3.67 MBAdobe PDFThumbnail
View/Open


This item is licensed under a Creative Commons License Creative Commons