Chondroitin Sulfate Impairs Neural Stem Cell Migration Through ROCK Activation.

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.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Galindo LT,Mundim MTVV,Pinto AS,Chiarantin GMD,Almeida MES,Lamers ML,Horwitz AR,Santos MF,Porcionatto M

doi

10.1007/s12035-017-0565-8

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

3185-3195

issue

4

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-017-0565-8

journal_volume

55

pub_type

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