PDF(Pubmed)
Abstract：
Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by deficiency of the survival motor neuron (SMN) protein. Although SMA is a genetic disease, environmental factors contribute to disease progression. Common pathogen components such as lipopolysaccharides (LPS) are considered significant contributors to inflammation and have been associated with muscle atrophy, which is considered a hallmark of SMA. In this study, we used the SMNΔ7 experimental mouse model of SMA to scrutinize the effect of systemic LPS administration, a strong pro-inflammatory stimulus, on disease outcome. Systemic LPS administration promoted a reduction in SMN expression levels in CNS, peripheral lymphoid organs, and skeletal muscles. Moreover, peripheral tissues were more vulnerable to LPS-induced damage compared to CNS tissues. Furthermore, systemic LPS administration resulted in a profound increase in microglia and astrocytes with reactive phenotypes in the CNS of SMNΔ7 mice. In conclusion, we hereby show for the first time that systemic LPS administration, although it may not precipitate alterations in terms of deficits of motor functions in a mouse model of SMA, it may, however, lead to a reduction in the SMN protein expression levels in the skeletal muscles and the CNS, thus promoting synapse damage and glial cells\' reactive phenotype.
摘要：
脊髓性肌萎缩症（SMA）是一种由运动神经元存活蛋白（SMN）缺乏引起的神经退行性疾病。虽然SMA是一种遗传性疾病,环境因素有助于疾病进展。常见的病原体成分如脂多糖（LPS）被认为是炎症的重要贡献者，并且与肌肉萎缩有关。这被认为是SMA的标志。在这项研究中,我们使用SMA的SMNΔ7实验小鼠模型来仔细检查全身LPS给药的效果，强烈的促炎刺激,关于疾病的结果。全身性LPS给药促进中枢神经系统中SMN表达水平的降低，外周淋巴器官，和骨骼肌。此外，与CNS组织相比,外周组织更容易受到LPS诱导的损伤.此外，全身LPS给药导致SMNΔ7小鼠CNS中具有反应性表型的小胶质细胞和星形胶质细胞的显着增加。总之,我们在此首次展示全身LPS给药，尽管它可能不会导致SMA小鼠模型中运动功能缺陷的改变，它可能，然而,导致骨骼肌和中枢神经系统中SMN蛋白表达水平降低，从而促进突触损伤和神经胶质细胞反应表型。
