NCAM-mediated locomotor recovery from spinal cord contusion injury involves neuroprotection, axon regeneration, and synaptogenesis.
The expression level of neural cell adhesion molecule (NCAM), which plays a critical role in pathways involving development and plasticity of the nervous system, changes markedly after spinal cord injury (SCI). However, the significance of NCAM-involved mechanisms in SCI remains elusive. The present study demonstrates that NCAM-deficient (ND) mice exhibited significantly poorer locomotor activity than wildtype (WT) littermates with the same injury intensity by the contusion model. To determine detailed contribution of NCAM, quantitative immunohistochemistry examination was performed on the injured spinal cord of 6mm along the rostrocaudal axis in the animals for up to 5 weeks after SCI. Overall level of NCAM decreased initially in the lesion site but increased around the center of the injury thereafter. At acute stage, more apoptotic cells were found in the gray and white matter in ND mice. Between the two animal groups, no obvious difference in expression levels of GFAP (astrocytosis marker) and MBP (remyelination marker) was detected. However, diverse expression trends of NF200 (axon marker), GAP-43 (synaptogenesis indicator) and phosphorylated ERK (active signal molecule) were observed in the area encompassing the lesion site, and remarkable differences were illustrated between WT mice and ND littermates. Detailed analysis indicates that NCAM-mediated pathways may be involved in the activation of ERK at acute stages and bi-phasic upregulation of GAP-43 expression at acute and sub-acute stages after SCI to promote cell survival, outgrowth of regenerated axons, synaptogenesis, and function recovery.
Zhang
Si
S
School of Biological Science, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
Xia
Yin Yan
YY
Lim
Han Chi
HC
Tang
Feng Ru
FR
Feng
Zhi Wei
ZW
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005260:Female; D005911:Gliosis / Q000473:pathology; D020439:Growth Cones / Q000473:pathology* / Q000502:physiology / Q000648:ultrastructure; D006614:Hindlimb / Q000294:innervation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D013569:Synapses / Q000502:physiology
D019006:Neural Cell Adhesion Molecules; D048049:Extracellular Signal-Regulated MAP Kinases