Induced NB-3 Limits Regenerative Potential of Serotonergic Axons after Complete Spinal Transection.

Abstract

NB-3 (contactin-6) is a member of the contactin family and has a wide range of roles during central nervous system development and disease. Here, we found that NB-3 was simultaneously induced in the serotonergic raphespinal tract (sRST) axons and in the scar-forming cells after spinal cord injury (SCI). Regrowth of sRST axons was promoted in vivo by blocking NB-3 expression in either sRST axons or scar-forming cells when post-traumatic axons of the sRST tried to penetrate the glial scar. NB-3 deficiency promoted synapse reformation between sRST regenerative axons and motor neurons and enhanced the potential for electrical activity of muscle contraction and motor coordination. In vivo evidence also suggested that NB-3 induction in both sRST axons and scar-forming cells was required to mediate NB-3 signaling inhibition of sRST axon regeneration after SCI. Our findings suggest that NB-3 protein is a potential molecular target for future SCI treatments.