Departamento de Fisiología, Facultad de Biología, Universidad de Sevilla, Seville, Spain.
Brain Struct Funct. 2020 Apr;225(3):1033-1053. doi: 10.1007/s00429-020-02057-y. Epub 2020 Mar 18.
Motoneurons of the oculomotor system show lesser vulnerability to neurodegeneration compared to other cranial motoneurons, as seen in amyotrophic lateral sclerosis (ALS). The overexpression of vascular endothelial growth factor (VEGF) is involved in motoneuronal protection. As previously shown, motoneurons innervating extraocular muscles present a higher amount of VEGF and its receptor Flk-1 compared to facial or hypoglossal motoneurons. Therefore, we aimed to study the possible sources of VEGF to brainstem motoneurons, such as glial cells and target muscles. We also studied the regulation of VEGF in response to axotomy in ocular, facial, and hypoglossal motor nuclei. Basal VEGF expression in astrocytes and microglial cells of the cranial motor nuclei was low. Although the presence of VEGF in the different target muscles for brainstem motoneurons was similar, the presynaptic element of the ocular neuromuscular junction showed higher amounts of Flk-1, which could result in greater efficiency in the capture of the factor by oculomotor neurons. Seven days after axotomy, a clear glial reaction was observed in all the brainstem nuclei, but the levels of the neurotrophic factor remained low in glial cells. Only the injured motoneurons of the oculomotor system showed an increase in VEGF and Flk-1, but such an increase was not detected in axotomized facial or hypoglossal motoneurons. Taken together, our findings suggest that the ocular motoneurons themselves upregulate VEGF expression in response to lesion. In conclusion, the low VEGF expression observed in glial cells suggests that these cells are not the main source of VEGF for brainstem motoneurons. Therefore, the higher VEGF expression observed in motoneurons innervating extraocular muscles is likely due either to the fact that this factor is more avidly taken up from the target muscles, in basal conditions, or is produced by these motoneurons themselves, and acts in an autocrine manner after axotomy.
与肌萎缩性侧索硬化症（ALS）相比，眼运动系统的运动神经元对神经退行性变的敏感性较低。血管内皮生长因子（VEGF）的过表达与运动神经元保护有关。如前所述，支配眼外肌的运动神经元表达的 VEGF 及其受体 Flk-1 明显高于面神经或舌下神经运动神经元。因此，我们旨在研究 VEGF 向脑干运动神经元的可能来源，如神经胶质细胞和靶肌肉。我们还研究了 VEGF 对眼、面和舌下运动核中轴突切断的反应调节。颅神经运动核中星形胶质细胞和小胶质细胞的基础 VEGF 表达水平较低。尽管脑干运动神经元的不同靶肌肉中都存在 VEGF，但眼运动神经元神经肌肉接头的突触前成分显示出更高水平的 Flk-1，这可能导致运动神经元更有效地捕获该因子。轴突切断后 7 天，所有脑干核中均观察到明显的神经胶质反应，但神经胶质细胞中的神经营养因子水平仍较低。只有眼运动系统的受损运动神经元才会增加 VEGF 和 Flk-1 的表达，但在轴突切断的面神经或舌下神经运动神经元中未检测到这种增加。综上所述，我们的研究结果表明，眼运动神经元本身会在受到损伤时上调 VEGF 的表达。总之，神经胶质细胞中观察到的低 VEGF 表达表明这些细胞不是脑干运动神经元 VEGF 的主要来源。因此，支配眼外肌的运动神经元中观察到的较高 VEGF 表达可能是由于在基础条件下该因子更强烈地从靶肌肉摄取，或者是由这些运动神经元本身产生的，并且在轴突切断后以自分泌方式发挥作用。
