Activation of Neurogenesis in Multipotent Stem Cells CulturedIn Vitroand in the Spinal Cord Tissue After Severe Injury by Inhibition of Glycogen Synthase Kinase-3
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F20%3A00538918" target="_blank" >RIV/68378041:_____/20:00538918 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/article/10.1007/s13311-020-00928-0" target="_blank" >https://link.springer.com/article/10.1007/s13311-020-00928-0</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s13311-020-00928-0" target="_blank" >10.1007/s13311-020-00928-0</a>
Alternative languages
Result language
angličtina
Original language name
Activation of Neurogenesis in Multipotent Stem Cells CulturedIn Vitroand in the Spinal Cord Tissue After Severe Injury by Inhibition of Glycogen Synthase Kinase-3
Original language description
The inhibition of glycogen synthase kinase-3 (GSK-3) can induce neurogenesis, and the associated activation of Wnt/beta-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 inhibitionin vitroon 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) andin vivoon 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 beta-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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Neurotherapeutics
ISSN
1933-7213
e-ISSN
1878-7479
Volume of the periodical
18
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
19
Pages from-to
515-533
UT code for WoS article
000574082500001
EID of the result in the Scopus database
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