Chondroitin Sulfate Impairs Neural Stem Cell Migration Through ROCK Activation

Chondroitin Sulfate Impairs Neural Stem Cell Migration Through ROCK Activation

Author Galindo, Layla Testa Autor UNIFESP Google Scholar
Mundim, Mayara T. V. V. Autor UNIFESP Google Scholar
Pinto, Agnes S. Autor UNIFESP Google Scholar
Chiarantin, Gabrielly Maria Denadai Autor UNIFESP Google Scholar
Almeida, Maira E. S. Google Scholar
Lamers, Marcelo L. Google Scholar
Horwitz, Alan R. Google Scholar
Santos, Marinilce F. Google Scholar
Porcionatto, Marimélia Aparecida Autor UNIFESP Google Scholar
Abstract Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG glycosaminoglycan side chains composed of chondroitin sulfate (CS) are responsible for its inhibitory activity on neurite outgrowth and are dependent on RhoA activation. Here, we hypothesize that CSPG also impairs neural stem cell migration inhibiting their penetration into an injury site. We show that DCX+ neuroblasts do not penetrate a CSPG-rich injured area probably due to Nogo receptor activation and RhoA/ROCK signaling pathway as we demonstrate in vitro with neural stem cells cultured as neurospheres and pull-down for RhoA. Furthermore, CS-impaired cell migration in vitro induced the formation of large mature adhesions and altered cell protrusion dynamics. ROCK inhibition restored migration in vitro as well as decreased adhesion size.
Keywords Neural stem cell
Cell migration
Chondroitin sulfate
Traumatic brain injury
RhoA
Rock
xmlui.dri2xhtml.METS-1.0.item-coverage Totowa
Language English
Sponsor Fundacao de Amparo a Pesquisa de Sao Paulo - FAPESP [2011/00526-7, 2012/00652]
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico - CNPq [404,646/2012-3]
National Institute of General Medical Sciences [GM23244]
Date 2018
Published in Molecular Neurobiology. Totowa, v. 55, n. 4, p. 3185-3195, 2018.
ISSN 0893-7648 (Sherpa/Romeo, impact factor)
Publisher Humana Press Inc
Extent 3185-3195
Origin http://dx.doi.org/10.1007/s12035-017-0565-8
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000427097500037
URI https://repositorio.unifesp.br/handle/11600/55794

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