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Mol Neurobiol. 2018 Apr;55(4):3185-3195. doi: 10.1007/s12035-017-0565-8. Epub 2017 May 5.

Chondroitin Sulfate Impairs Neural Stem Cell Migration Through ROCK Activation.

Author information

1
Department of Biochemistry, Laboratory of Neurobiology, Universidade Federal de São Paulo, Rua Pedro de Toledo, 669 - 3o andar, São Paulo, SP, 04039-032, Brazil.
2
Physiopathology Laboratory, Butantan Institute, São Paulo, 05503-900, Brazil.
3
Department of Morphological Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, 90050-170, Brazil.
4
Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, 22903, USA.
5
Department of Cell and Developmental Biology, Biomedical Sciences Institute, Universidade de São Paulo, São Paulo, 05508-000, Brazil.
6
Department of Biochemistry, Laboratory of Neurobiology, Universidade Federal de São Paulo, Rua Pedro de Toledo, 669 - 3o andar, São Paulo, SP, 04039-032, Brazil. marimelia.porcionatto@unifesp.br.

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:

Cell migration; Chondroitin sulfate; Neural stem cell; RhoA; Rock; Traumatic brain injury

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