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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Chondroitin Sulfate Impairs Neural Stem Cell Migration Through ROCK Activation

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Author(s):
Galindo, Layla T. [1] ; Mundim, Mayara T. V. V. [1] ; Pinto, Agnes S. [1] ; Chiarantin, Gabrielly M. D. [1] ; Almeida, Maira E. S. [2] ; Lamers, Marcelo L. [3] ; Horwitz, Alan R. [4] ; Santos, Marinilce F. [5] ; Porcionatto, Marimelia [1]
Total Authors: 9
Affiliation:
[1] Univ Fed Sao Paulo, Dept Biochem, Neurobiol Lab, Rua Pedro de Toledo 669, 3 Andar, BR-04039032 Sao Paulo, SP - Brazil
[2] Butantan Inst, Physiopathol Lab, BR-05503900 Sao Paulo - Brazil
[3] Univ Fed Rio Grande do Sul, Dept Morphol Sci, BR-90050170 Porto Alegre, RS - Brazil
[4] Univ Virginia, Dept Cell Biol, Sch Med, Charlottesville, VA 22903 - USA
[5] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, BR-05508000 Sao Paulo - Brazil
Total Affiliations: 5
Document type: Journal article
Source: Molecular Neurobiology; v. 55, n. 4, p. 3185-3195, APR 2018.
Web of Science Citations: 6
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. (AU)

FAPESP's process: 11/00526-7 - Study of the role of Rho GTPases family members in the control of neuroblast migration
Grantee:Layla Testa Galindo
Support Opportunities: Scholarships in Brazil - Doctorate