Assessment of functional recovery and axonal sprouting in oligodendrocyte-myelin glycoprotein (OMgp) null mice after spinal cord injury

摘要

Oligodendrocyte-myelin glycoprotein (OMgp) is a myelin component that has been shown in vitro to inhibit neurite outgrowth by binding to the Nogo-66 receptor (NgR1)/Lingo-1/Taj (TROY)/p75 receptor complex to activate the RhoA pathway. To investigate the effects of OMgp on axon regeneration in vivo, OMgp^-/- mice on a mixed 129/Sv/C57BL/6 (129BL6) or a C57BL/6 (BL6) genetic background were tested in two spinal cord injury (SCI) models — a severe complete transection or a milder dorsal hemisection. OMgp^-/- mice on the mixed 129BL6 genetic background showed greater functional improvement compared to OMgp^+/+ littermates, with increased numbers of cholera toxin B-labeled ascending sensory axons and 5-HT⁺ descending axons and less RhoA activation after spinal cord injury. Myelin isolated from OMgp^-/- mice (129BL6) was significantly less inhibitory to neurite outgrowth than wild-type (wt) myelin in vitro. However, OMgp^-/- mice on a BL/6 genetic background showed neither statistically significant functional recovery nor axonal sprouting following dorsal hemisection.