Inhibition of the Rho signaling pathway improves neurite outgrowth and neuronal differentiation of mouse neural stem cells

• Type of Material: Article
• Authors: Haigang Gu, Emory University; Shan Ping Yu, Emory University; Claire-Anne Gutekunst, Emory University; Robert E. Gross, Emory University; Ling Wei, Emory University
• Language: English
• Date: 2013
• Publisher: e-Century Publishing
• Publication Version: Final Published Version
• Copyright Statement: IJPPP Copyright © 2013
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): http://www.ijppp.org/V5_No1.html
• Title of Journal or Parent Work: International Journal of Physiology, Pathophysiology and Pharmacology
• ISSN: 1944-8171
• Volume: 5
• Issue: 1
• Start Page: 11
• End Page: 20
• Grant/Funding Information: This work was supported by NIH grants NS 045810 (L.W.), NS062097 (L.W.), NS 058710 (L.W.), NS057255 (S.P.Y.), NS46322 (R.E.G), a grant from the Atlanta Clinical and Translational Science Institute (R.E.G., L.W. and C.A.G) and the American Heart Association Established Investigator Award (LW). It was also supported by the NIH grant NS055077 to the ENNCF (Emory Neurology-NINDS Core Facility).
• Keywords: Rho signaling pathway; myelin; neurite outgrowth; Neural stem cells; neuronal differentiation
• Research Categories: Engineering, Biomedical

Abstract

Neurons in the adult mammalian CNS do not spontaneously regenerate axons after injury due to CNS myelin and other inhibitory factors. Previous studies have showed that inhibition of the Rho-ROCK pathway promotes axonal outgrowth in primary neurons or in spinal cord injury models. Furthermore, RhoA inhibitor C3 transferase has a potential effect to induce neural differentiation in primary cultured neurons and cell lines. As stem cells and stem cell-derived neural progenitor cells have emerged as a regenerative medicine for stroke, Parkinson’s disease and other neurological disorders, strategies that can promote axonal outgrowth and neuronal differentiation appear to have promising benefits in the cell-based therapy. Currently, how changes in the Rho-ROCK pathway may affect the neurite outgrowth and neuronal differentiation of stem cells has been poorly understood. The present investigation examined the effects of RhoA inhibition on neurite outgrowth and neuronal differentiation of neural stem cells (NSCs) isolated from the subventricular zone (SVZ) of the mouse. Our results show that inhibition of RhoA leads to neurite outgrowth of NSCs not only on normal culture substrate, poly-D-lysine (PDL), but also on myelin substrate. Moreover, inhibition of RhoA improves neuronal differentiation of NSCs and up-regulates biomarkers of neuronal gene expression. These results support that the Rho signaling pathway plays an important role in neurite development and neuronal differentiation of NSCs.