PT  - JOURNAL ARTICLE
AU  - Karin Löw
AU  - Maya Culbertson
AU  - Frank Bradke
AU  - Marc Tessier-Lavigne
AU  - Mark H. Tuszynski
TI  - Netrin-1 Is a Novel Myelin-Associated Inhibitor to Axon Growth
AID  - 10.1523/JNEUROSCI.4906-07.2008
DP  - 2008 Jan 30
TA  - The Journal of Neuroscience
PG  - 1099--1108
VI  - 28
IP  - 5
4099  - http://www.jneurosci.org/content/28/5/1099.short
4100  - http://www.jneurosci.org/content/28/5/1099.full
SO  - J. Neurosci.2008 Jan 30; 28
AB  - We investigated the influence of the bifunctional guidance molecule netrin-1 on axonal growth in the injured adult spinal cord. In the adult, netrin-1 is expressed on mature oligodendrocytes, cells of the central canal, and the meninges. Netrin-1 protein in white matter is selectively enriched adjacent to paranodal loops of myelin in nodes of Ranvier. The repulsion-mediating netrin-1 uncoordinated-5 (UNC5) receptors are expressed by neurons of the corticospinal and rubrospinal projections, and by intrinsic neurons of the spinal cord, both before and after spinal cord injury. Neutralization of netrin-1 in myelin prepared from adult rat spinal cord using UNC5 receptor bodies increases neurite outgrowth from UNC5-expressing spinal motor neurons in vitro. Furthermore, axon regeneration is inhibited in a netrin-1-enriched zone, devoid of other myelin-associated inhibitors, within spinal cord lesion sites in vivo. We conclude that netrin-1 is a novel oligodendrocyte-associated inhibitor that can contribute to axonal growth failure after adult spinal cord injury.