Zheng Chengyun, Sköld Mattias K, Li Jian, Nennesmo Inger, Fadeel Bengt, Henter Jan-Inge
Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Biochem Biophys Res Commun. 2007 Nov 30;363(4):989-93. doi: 10.1016/j.bbrc.2007.09.088. Epub 2007 Oct 1.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease resulting from motor neuron loss in the spinal cord and brain stem. In the present study, we found that systemic administration of recombinant vascular endothelial growth factor (VEGF) significantly diminished astrogliosis and increased the number of neuromuscular junctions in a Cu/Zn superoxide dismutase (SOD1) transgenic mouse model of ALS. Our results thus demonstrate a novel regulatory role of VEGF on astrocytes and are suggestive of protective effects of VEGF both in the peripheral and central nervous system in the SOD1 transgenic mouse model. These findings warrant further evaluation of the mechanism(s) of regulatory effects of VEGF on neuronal and non-neuronal cells, and the relation of these events to motor neuron degeneration and the onset and progression of ALS.
肌萎缩侧索硬化症(ALS)是一种由脊髓和脑干运动神经元丧失导致的致命性神经退行性疾病。在本研究中,我们发现,在ALS的铜/锌超氧化物歧化酶(SOD1)转基因小鼠模型中,全身给予重组血管内皮生长因子(VEGF)可显著减轻星形胶质细胞增生,并增加神经肌肉接头的数量。因此,我们的结果证明了VEGF对星形胶质细胞具有新的调节作用,并提示VEGF在SOD1转基因小鼠模型的外周和中枢神经系统中均具有保护作用。这些发现值得进一步评估VEGF对神经元和非神经元细胞的调节作用机制,以及这些事件与运动神经元变性及ALS的发病和进展之间的关系。