Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
J Biol Chem. 2011 Jan 21;286(3):1876-83. doi: 10.1074/jbc.M110.163493. Epub 2010 Nov 18.
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 wild-type 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 knock-out is not sufficient to induce extensive axonal regeneration after spinal cord injury.
髓鞘中的抑制轴突再生的成分被认为是导致成年中枢神经系统轴突再生缺乏的主要原因。髓鞘中存在三种能抑制神经突生长的蛋白：Nogo、髓鞘相关糖蛋白和少突胶质细胞髓鞘糖蛋白。所有这些蛋白都与相同的受体相互作用，即 Nogo 受体（NgR）和配对免疫球蛋白样受体 B（PIR-B）。根据之前的报告，在脊髓损伤后，NgR 敲除小鼠的皮质脊髓束（CST）再生并未增强。因此，我们评估了 PIR-B 敲除小鼠的 CST 再生情况。我们发现，在脊髓背侧半切后，PIR-B 敲除小鼠和野生型小鼠的后肢运动功能（通过 Basso 小鼠量表、足迹测试、斜面测试和平衡木行走测试评估）没有差异。此外，损伤后 CST 纤维的追踪显示，PIR-B 敲除小鼠的 CST 中没有增强的轴突再生或发芽。将 NgR 拮抗剂 NEP1-40 全身给予 PIR-B 敲除小鼠，并未增强再生反应。这些结果表明，PIR-B 敲除不足以诱导脊髓损伤后的广泛轴突再生。
