Departamento de Fisiología, Facultad de Biología, Universidad de Sevilla, 41012 Sevilla, Spain.
Departamento de Fisiología, Facultad de Biología, Universidad de Sevilla, 41012 Sevilla, Spain
J Neurosci. 2014 May 14;34(20):7007-17. doi: 10.1523/JNEUROSCI.4231-13.2014.
Transplants of neural progenitor cells (NPCs) into the injured CNS have been proposed as a powerful tool for brain repair, but, to date, few studies on the physiological response of host neurons have been reported. Therefore, we explored the effects of NPC implants on the discharge characteristics and synaptology of axotomized abducens internuclear neurons, which mediate gaze conjugacy for horizontal eye movements. NPCs were isolated from the subventricular zone of neonatal cats and implanted at the site of transection in the medial longitudinal fascicle of adult cats. Abducens internuclear neurons of host animals showed a complete restoration of axotomy-induced alterations in eye position sensitivity, but eye velocity sensitivity was only partially regained. Analysis of the inhibitory and excitatory components of the discharge revealed a normal re-establishment of inhibitory inputs, but only partial re-establishment of excitatory inputs. Moreover, their inhibitory terminal coverage was similar to that in controls, indicating that there was ultimately no loss of inhibitory synaptic inputs. Somatic coverage by synaptophysin-positive contacts, however, showed intermediate values between control animals and animals that had undergone axotomy, likely due to partial loss of excitatory inputs. We also demonstrated that severed axons synaptically contacted NPCs, most of which were VEGF immunopositive, and that abducens internuclear neurons expressed the VEGF receptor Flk1. Together, our results suggest that VEGF neurotrophic support might underlie the increased inhibitory-to-excitatory balance observed in the postimplant cells. The noteworthy improvement of firing properties of injured neurons following NPC implants indicates that these cells might provide a promising therapeutic strategy after neuronal lesions.
将神经祖细胞 (NPC) 移植到受损的中枢神经系统中被提议作为修复大脑的有力工具，但迄今为止，很少有关于宿主神经元生理反应的研究报道。因此，我们研究了 NPC 植入对介导水平眼球运动共轭的外展神经核间神经元轴突切断后的放电特征和突触结构的影响。NPC 是从新生猫的侧脑室下区分离出来的，并植入成年猫的内侧纵束横断部位。宿主动物的外展神经核间神经元完全恢复了轴突切断引起的眼位置敏感性改变，但眼速度敏感性仅部分恢复。对放电的抑制和兴奋成分的分析表明，抑制性输入得到了正常的重建，但兴奋性输入仅部分重建。此外，它们的抑制性末端覆盖与对照动物相似，表明最终没有抑制性突触输入的丢失。然而，突触小体蛋白阳性接触的体覆盖显示出介于对照动物和经历过轴突切断的动物之间的中间值，这可能是由于兴奋性输入的部分丧失。我们还证明了被切断的轴突与 NPC 形成突触接触，其中大多数 NPC 呈 VEGF 免疫阳性，并且外展神经核间神经元表达 VEGF 受体 Flk1。总之，我们的结果表明，VEGF 神经营养支持可能是植入后细胞中观察到的抑制性到兴奋性平衡增加的基础。NPC 植入后损伤神经元放电特性的显著改善表明，这些细胞可能为神经元损伤后的治疗策略提供了有希望的选择。
