Amelioration of spinal cord injury by the regulation of neurotmphin receptor p75-mediated signaling

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1. Analysis of alteration of gene expression after spinal cord injuryGenes of which expression were altered in the injured spinal cord were analyzed by the DNA array method. The 46 genes including inflammatory cytokines or lymphokines were upregulated and 18 genes involving ion transporter or amino acid transporter were downregulated. We focused on and analyzed some genes related to p75NTR signaling.2 Evaluation of the peptides that suppress the p75NTR-induced negative signals.a) A peptide expected to inhibit the binding between RhoGDI and p75, and b) the peptide expected to inhibit the binding between sortilin and pro-brain-derived neurotrophic factor (BDNF) were examined their activities on the locomotion activity after spinal cord injury. However, both peptides failed to improve the locomotion activity. Various proteases induced in the injury site of the spinal cord may be responsible for the degradation of the peptides.3 Amelioration of the spinal cord injury in p75NTR gene-modifie … More d animalsThe improvement of locomotion activity after spinal cord injury was compared between p75NTR gene-disrupted mouse (KO mouse) and wild mouse. KO mouse gave higher scores of the locomotion activity than wild mouse for the first 8 days, but the difference was disappeared thereinafter, suggesting that p75NTR signal disturbs the restoration at early stages of the damage.4 Development of the conditional p75NTR transgenic (Tg) mouseThe vector DNA containing a stop codon between loxp genes and the p75NTR gene in the down stream was constructed, and transferred to fertilized eggs. Because the introduced p75NTR gene does not express as long as stop codon between loxp is not deleted, the maintenance of the animal is easy. If the transgenic mice expressing cre enzyme gene in a region-specicic manner were hybridized with this p75NTR Tg mouse, the p75NTR gene would express simultaneously in the cre enzyme expressing regions. This Tg animals would become useful tool to investigate p75NTR function in the future. Less