Centre for Research in Neuroscience, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Glia. 2010 Mar;58(4):423-33. doi: 10.1002/glia.20934.
Receptor protein tyrosine phosphatase sigma (RPTPsigma) plays a role in inhibiting axon growth during development. It has also been shown to slow axon regeneration after peripheral nerve injury and inhibit axon regeneration in the optic nerve. Here, we assessed the ability of the corticospinal tract (CST) axons to regenerate after spinal hemisection and contusion injury in RPTPsigma deficient (RPTPsigma(-/-)) mice. We show that damaged CST fibers in RPTPsigma(-/-) mice regenerate and appear to extend for long distances after a dorsal hemisection or contusion injury of the thoracic spinal cord. In contrast, no long distance axon regeneration of CST fibers is seen after similar lesions in wild-type mice. In vitro experiments indicate that cerebellar granule neurons from RPTPsigma(-/-) mice have reduced sensitivity to the inhibitory effects of chondroitin sulfate proteoglycan (CSPG) substrate, but not myelin, which may contribute to the growth of CST axons across the CSPG-rich glial scar. Our data suggest that RPTPsigma may function to prevent axonal growth after injury in the adult mammalian spinal cord and could be a target for promoting long distance regeneration after spinal cord injury.
受体酪氨酸磷酸化酶 sigma（RPTPsigma）在发育过程中抑制轴突生长中起作用。它也被证明可以减缓周围神经损伤后的轴突再生，并抑制视神经中的轴突再生。在这里，我们评估了 RPTPsigma 缺陷（RPTPsigma(-/-)）小鼠脊髓半切和挫伤损伤后皮质脊髓束（CST）轴突再生的能力。我们发现，在胸段脊髓背侧半切或挫伤损伤后，RPTPsigma(-/-)小鼠受损的 CST 纤维会再生，并似乎可以延伸很长距离。相比之下，在野生型小鼠中，不会看到 CST 纤维的长距离轴突再生。体外实验表明，来自 RPTPsigma(-/-)小鼠的小脑颗粒神经元对软骨素硫酸盐蛋白聚糖（CSPG）底物的抑制作用的敏感性降低，但对髓鞘的敏感性没有降低，这可能有助于 CST 轴突穿过富含 CSPG 的神经胶质瘢痕生长。我们的数据表明，RPTPsigma 可能在成年哺乳动物脊髓损伤后防止轴突生长，并可能成为促进脊髓损伤后长距离再生的靶点。
