Universität zu Köln

Joshi, Abhijeet R., Bobylev, Ilja, Zhang, Gang, Sheikh, Kazim A. and Lehmann, Helmar C. (2015). Inhibition of Rho-kinase differentially affects axon regeneration of peripheral motor and sensory nerves. Exp. Neurol., 263. S. 28 - 39. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1090-2430

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Abstract

The small GTPase RhoA and its down-stream effector Rho-kinase (ROCK) are important effector molecules of the neuronal cytoskeleton. Modulation of the RhoA/ROCK pathway has been shown to promote axonal regeneration, however in vitro and animal studies are inconsistent regarding the extent of axonal outgrowth induced by pharmacological inhibition of ROCK. We hypothesized that injury to sensory and motor nerves result in diverse activation levels of RhoA, which may impact the response of those nerve fiber modalities to ROCK inhibition. We therefore examined the effects of Y-27632, a chemical ROCK inhibitor, on the axonal outgrowth of peripheral sensory and motor neurons grown in the presence of growth-inhibiting chondroitin sulfate proteoglycans (CSPGs). In addition we examined the effects of three different doses of Y-27632 on nerve regeneration of motor and sensory nerves in animal models of peripheral nerve crush. In vitro, sensory neurons were less responsive to Y-27632 compared to motor neurons in a non-growth permissive environment. These differences were associated with altered expression and activation of RhoA in sensory and motor axons. In vivo, systemic treatment with high doses of Y-27632 significantly enhanced the regeneration of motor axons over short distances, while the regeneration of sensory fibers remained largely unchanged. Our results support the concept that in a growth non-permissive environment, the regenerative capacity of sensory and motor axons is differentially affected by the RhoA/ROCK pathway, with motor neurons being more responsive compared to sensory. Future treatments, that are aimed to modulate RhoA activity, should consider this functional diversity. (C) 2014 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Joshi, Abhijeet R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bobylev, Ilja UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhang, Gang UNSPECIFIED UNSPECIFIED UNSPECIFIED Sheikh, Kazim A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Helmar C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-418814
DOI:	10.1016/j.expneurol.2014.09.012
Journal or Publication Title:	Exp. Neurol.
Volume:	263
Page Range:	S. 28 - 39
Date:	2015
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication:	SAN DIEGO
ISSN:	1090-2430
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHONDROITIN SULFATE PROTEOGLYCAN; SPINAL-CORD-INJURY; SIGNALING PATHWAY; NEURONS; GTPASE; MOUSE; CELLS; CNS; INACTIVATION; DEGRADATION Multiple languages Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41881