Ameliorative Effects of p75NTR-ED-Fc on Axonal Regeneration and Functional Recovery in Spinal Cord-Injured Rats

• Published in: Molecular neurobiology 2015-12, Vol.52 (3), p.1821-1834
• Main Authors: Wang, Yong-Tang, Lu, Xiu-Min, Zhu, Feng, Huang, Peng, Yu, Ying, Long, Zai-Yun, Wu, Ya-Min
• Format: Article
• Language: English
• Subjects: Animals; Axons - metabolism; Biomedical and Life Sciences; Biomedicine; Cell Biology; Disease Models, Animal; Female; Immunoglobulins; Myelin Proteins - metabolism; Myelin Sheath - metabolism; Nerve Regeneration - physiology; Neurobiology; Neurology; Neurons; Neurosciences; Polymerase chain reaction; Proteins; Rats, Sprague-Dawley; Receptor, Nerve Growth Factor - metabolism; Recovery of Function - physiology; Rodents; Spinal Cord - metabolism; Spinal Cord - physiopathology; Spinal cord injuries; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - physiopathology
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-014-8972-6

As a co-receptor of Nogo-66 receptor (NgR) and a critical receptor for paired immunoglobulin-like receptor (PirB), p75 neurotrophin receptor (p75NTR) mediates the inhibitory effects of myelin-associated inhibitors on axonal regeneration after spinal cord injury. Therefore, the p75NTR antagonist, such as recombinant p75NTR protein or its homogenates may block the inhibitory effects of myelin and promote the axonal regeneration and functional recovery. The purposes of this study are to subclone and express the extracellular domain gene of human p75NTR with IgG-Fc (hp75NTR-ED-Fc) in prokaryotic expression system and investigate the effects of the recombinant protein on axonal regeneration and functional recovery in spinal cord-injured rats. The hp75NTR-ED-Fc coding sequence was amplified from pcDNA-hp75NTR-ED-Fc by polymerase chain reaction (PCR) and subcloned into vector pET32a (+), then the effects of the purified recombinant protein on neurite outgrowth of dorsal root ganglion (DRG) neurons cultured with myelin-associated glycoprotein (MAG) were determined, and the effects of the fusion protein on axonal regeneration, functional recovery, and its possible mechanisms in spinal cord-injured rats were further investigated. The results indicated that the purified infusion protein could promote neurite outgrowth of DRG neurons, promote axonal regeneration and functional recovery, and decrease RhoA activation in spinal cord-injured rats. Taken together, the findings revealed that p75NTR still may be a potential and novel target for therapeutic intervention for spinal cord injury and that the hp75NTR-ED-Fc fusion protein treatment enhances functional recovery by limiting tissue loss and stimulating axonal growth in spinal cord-injured rats, which may result from decreasing the activation of RhoA.