Synaptic loss and firing alterations in Axotomized Motoneurons are restored by vascular endothelial growth factor (VEGF) and VEGF-B
Synaptic loss and firing alterations in Axotomized Motoneurons are restored by vascular endothelial growth factor (VEGF) and VEGF-B
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DOI：
10.1016/j.expneurol.2018.03.004
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发表时间：
2018-06-01
影响因子：
5.3
通讯作者：
Pastor, Angel M.
中科院分区：
文献类型：
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作者：
Calvo, Paula M.;de la Cruz, Rosa R.;Pastor, Angel M.
血管内皮生长因子（VEGF），也称为VEGF-A，因其血管生成和血管生成活性而被发现，但后来证明VEGF对病变和疾病具有神经保护作用。在运动神经元变性的不同模型中，VEGF给药导致运动神经元死亡显著减少。然而，没有关于备用运动神经元的生理状态的信息。我们研究了血管内皮生长因子对轴突切断的运动神经元的营养作用与记录在警觉的动物使用眼神经系统作为实验模型，辅之以共聚焦显微镜水平的突触研究。轴突切断导致外展神经运动神经元放电特征的急剧改变，以及突触输入的大量丢失。逆行递送VEGF完全恢复了受损运动神经元的放电活动和突触驱动信号，如运动神经元放电率与运动性能相关所示。此外，VEGF处理的运动神经元恢复了正常密度的运动神经元胞体周围的突触终扣和神经元，在轴突切断后发现的低水平的突触终端。VEGF还减少了展神经核轴突切断诱导的星形胶质细胞增生至对照值。施用VEGF-B产生与VEGF类似的结果。这是第一次证明VEGF和VEGF-B恢复受损运动神经元的正常操作模式和突触输入。总之，这些数据表明，这些分子是运动神经元相关的突触营养因子，并支持其治疗运动神经元疾病的临床潜力。
Vascular endothelial growth factor (VEGF), also known as VEGF-A, was discovered due to its vasculogenic and angiogenic activity, but a neuroprotective role for VEGF was later proven for lesions and disorders. In different models of motoneuronal degeneration, VEGF administration leads to a significant reduction of motoneuronal death. However, there is no information about the physiological state of spared motoneurons. We examined the trophic role of VEGF on axotomized motoneurons with recordings in alert animals using the oculomotor system as the experimental model, complemented with a synaptic study at the confocal microscopy level. Axotomy leads to drastic alterations in the discharge characteristics of abducens motoneurons, as well as to a substantial loss of their synaptic inputs. Retrograde delivery of VEGF completely restored the discharge activity and synaptically driven signals in injured motoneurons, as demonstrated by correlating motoneuronal firing rate with motor performance. Moreover, VEGF-treated motoneurons recovered a normal density of synaptic boutons around motoneuronal somata and in the neuropil, in contrast to the low levels of synaptic terminals found after axotomy. VEGF also reduced the astrogliosis induced by axotomy in the abducens nucleus to control values. The administration of VEGF-B produced results similar to those of VEGF. This is the first work demonstrating that VEGF and VEGF-B restore the normal operating mode and synaptic inputs on injured motoneurons. Altogether these data indicate that these molecules are relevant synaptotrophic factors for motoneurons and support their clinical potential for the treatment of motoneuronal disorders.