Paired Immunoglobulin-like Receptor B Knockout Does Not Enhance Axonal Regeneration or Locomotor Recovery after Spinal Cord Injury
Paired Immunoglobulin-like Receptor B Knockout Does Not Enhance Axonal Regeneration or Locomotor Recovery after Spinal Cord Injury
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DOI：
10.1074/jbc.m110.163493
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发表时间：
2011-01-21
影响因子：
4.8
通讯作者：
Yamashita, Toshihide
中科院分区：
文献类型：
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作者：
Nakamura, Yuka;Fujita, Yuki;Yamashita, Toshihide
抑制轴突再生的髓磷脂组分被认为显著地导致在成人中枢神经系统中注意到的轴突再生缺乏。在髓鞘中发现的三种蛋白质，Nogo，髓鞘相关糖蛋白和少突胶质细胞髓鞘糖蛋白，在体外抑制神经突生长。所有这些蛋白质与相同的受体，即Nogo受体（NgR）和成对的免疫球蛋白样受体B（PIR-B）相互作用。根据先前的报道，在脊髓损伤后NgR敲除小鼠中皮质脊髓束（CST）再生没有增强。因此，我们评估了PIR-B基因敲除小鼠的CST再生。我们发现，后肢运动功能，评估使用Basso小鼠量表，足迹测试，斜面测试，和梁行走测试，没有不同的PIR-B基因敲除和野生型小鼠脊髓背侧半切后。此外，在损伤后追踪CST纤维并没有发现PIR-B基因敲除小鼠的CST中轴突再生或发芽增强。NEP 1 -40，NgR拮抗剂，PIR-B基因敲除小鼠全身给药，没有增强再生反应。这些结果表明PIR-B基因敲除不足以诱导脊髓损伤后广泛的轴突再生。
Myelin components that inhibit axonal regeneration are believed to contribute significantly to the lack of axonal regeneration noted in the adult central nervous system. Three proteins found in myelin, Nogo, myelin-associated glycoprotein, and oligodendrocyte-myelin glycoprotein, inhibit neurite outgrowth in vitro. All of these proteins interact with the same receptors, namely, the Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PIR-B). As per previous reports, corticospinal tract (CST) regeneration is not enhanced in NgR-knock-out mice after spinal cord injury. Therefore, we assessed CST regeneration in PIR-B-knock-out mice. We found that hindlimb motor function, as assessed using the Basso mouse scale, footprint test, inclined plane test, and beam walking test, did not differ between the PIR-B-knock-out and wildtype mice after dorsal hemisection of the spinal cord. Further, tracing of the CST fibers after injury did not reveal enhanced axonal regeneration or sprouting in the CST of the PIR-B-knock-out mice. Systemic administration of NEP1-40, a NgR antagonist, to PIR-B knock-out mice did not enhance the regenerative response. These results indicate that PIR-B knockout is not sufficient to induce extensive axonal regeneration after spinal cord injury.