Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury.
Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury.
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DOI：
10.1016/j.celrep.2017.02.058
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发表时间：
2017-03-14
期刊：
影响因子：
8.8
通讯作者：
Cafferty WBJ
中科院分区：
文献类型：
--
作者：
Fink KL;López-Giráldez F;Kim IJ;Strittmatter SM;Cafferty WBJ
脊髓损伤（SCI）后功能缺陷持续存在，因为成年哺乳动物中枢神经系统（CNS）的轴突无法再生。然而，通常在创伤后观察到适度水平的自发功能恢复，并且认为是由完整电路的可塑性介导的。完整电路可塑性的机制尚未阐明。在这里，我们的特点在体内的转录组发芽完整的神经元从Ngr 1空小鼠后，部分SCI。我们确定了溶血磷脂酸信号调节剂LPPR1和LPAR1作为邻近损伤后完整皮质脊髓运动神经元的内在轴突生长调节剂。此外，在野生型小鼠单侧脑干损伤后，体内LPAR1抑制或LPPR1过表达增强了完整皮质脊髓束轴突的发芽，并产生了更大的功能恢复。因此，损伤诱导的完整神经元发芽的转录谱揭示了轴突生长起始和新突触形成的治疗增强的靶点。
Functional deficits persist after spinal cord injury (SCI) because axons in the adult mammalian central nervous system (CNS) fail to regenerate. However, modest levels of spontaneous functional recovery are typically observed after trauma and are thought to be mediated by the plasticity of intact circuitry. The mechanisms underlying intact circuit plasticity are not delineated. Here, we characterize the in vivo transcriptome of sprouting intact neurons from Ngr1 null mice after partial SCI. We identify the lysophosphatidic acid signaling modulators LPPR1 and LPAR1 as intrinsic axon growth modulators for intact corticospinal motor neurons after adjacent injury. Furthermore, in vivo LPAR1 inhibition or LPPR1 overexpression enhances sprouting of intact corticospinal tract axons and yields greater functional recovery after unilateral brainstem lesion in wild-type mice. Thus, the transcriptional profile of injury-induced sprouting of intact neurons reveals targets for therapeutic enhancement of axon growth initiation and new synapse formation.