Variable laterality of corticospinal tract axons that regenerate after spinal cord injury as a result of PTEN deletion or knock-down.
Variable laterality of corticospinal tract axons that regenerate after spinal cord injury as a result of PTEN deletion or knock-down.
复制标题
DOI：
10.1002/cne.23987
复制
发表时间：
2016-09-01
期刊：
影响因子：
--
通讯作者：
Steward O
中科院分区：
文献类型：
--
作者：
Willenberg R;Zukor K;Liu K;He Z;Steward O
皮质脊髓束（CST）轴突从一个半球通常延伸和终止主要在对侧脊髓。我们之前表明，删除感觉运动皮质中的PTEN能够使CST轴突在脊髓损伤后再生，并且一些再生轴突沿着“错误”侧延伸。在这里，我们的特点是程度的特异性再生方面的偏侧性。在新生的PTEN-融合小鼠中通过皮质AAV-Cre注射选择性删除PTEN。成年后，小鼠在T12时接受背侧半切损伤或在T9时接受完全挤压损伤。通过在具有脊髓损伤的PTEN缺失小鼠和未接受AAV-Cre的未损伤的PTEN-floxed小鼠中单侧BDA注射追踪来自一个半球的CST轴突。在未损伤的小鼠中，白色物质中97.9 ± 0.7%的BDA标记轴突和灰质中88.5 ± 1.0%的BDA标记轴突位于起源皮质的对侧。相比之下，由于PTEN缺失而延伸经过病变的CST轴突的偏侧性在动物中各不相同。在某些情况下，再生轴突主要在同侧延伸，在其他情况下，轴突主要向对侧延伸，在其他情况下，轴突在两侧的数量相似。类似的结果也出现在以前使用shRNA介导的PTEN敲低的研究中。这些结果表明，由于PTEN缺失或敲低而延伸经过病变的CST轴突不保持未受伤的CST的对侧规则，突出了再生轴突产生的电路如何不同于未受伤的CST的一个方面。
Corticospinal tract (CST) axons from one hemisphere normally extend and terminate predominantly in the contralateral spinal cord. We previously showed that deleting PTEN in the sensorimotor cortex enables CST axons to regenerate after spinal cord injury and that some regenerating axons extend along the “wrong” side. Here, we characterize the degree of specificity of regrowth in terms of laterality. PTEN was selectively deleted via cortical AAV-Cre injections in neonatal PTEN-floxed mice. As adults, mice received dorsal hemisection injuries at T12 or complete crush injuries at T9. CST axons from one hemisphere were traced by unilateral BDA injections in PTEN-deleted mice with spinal cord injury and in non-injured PTEN-floxed mice that had not received AAV-Cre. In non-injured mice, 97.9 ± 0.7% of BDA-labeled axons in white matter and 88.5 ± 1.0% of BDA-labeled axons in grey matter were contralateral to the cortex of origin. In contrast, laterality of CST axons that extended past a lesion due to PTEN deletion varied across animals. In some cases, regenerated axons extended predominantly on the ipsilateral side, in other cases, axons extended predominantly contralaterally, and in others, axons were similar in numbers on both sides. Similar results were seen in analyses of cases from previous studies using shRNA-mediated PTEN knock-down. These results indicate that CST axons that extend past a lesion due to PTEN deletion or knock-down do not maintain the contralateral rule of the non-injured CST, highlighting one aspect for how resultant circuitry from regenerating axons may differ from that of the uninjured CST.