Gowing Genevieve, Lalancette-Hébert Mélanie, Audet Jean-Nicolas, Dequen Florence, Julien Jean-Pierre
Centre de Recherche du Centre Hospitalier Universitaire de Québec, Department of Psychiatry and Neuroscience of Laval University, Quebec, Pavillon CHUL, 2705 Boulevard Laurier, Quebec, Canada.
Exp Neurol. 2009 Dec;220(2):267-75. doi: 10.1016/j.expneurol.2009.08.021. Epub 2009 Sep 3.
Macrophage colony stimulating factor (M-CSF) is a cytokine that regulates the survival, proliferation and maturation of microglial cells. Administration of M-CSF can promote neuronal survival in various models of central nervous system (CNS) injury. Here, in an attempt to induce a neuroprotective microglial cell phenotype and enhance motor neuron survival, mutant SOD1(G37R) transgenic mice were treated, weekly, with M-CSF starting at onset of disease. Unexpectedly, M-CSF accelerated disease progression in SOD1(G37R) mouse model of ALS. The shortened survival of M-CSF-treated animals was associated with diminished muscle innervation and enhanced adoption of a macrophage-like phenotype by microglial cells characterised by the upregulation of pro-inflammatory cytokines TNF-alpha and IL-1 beta and of the phagocytic marker CD68.
巨噬细胞集落刺激因子（M-CSF）是一种调节小胶质细胞存活、增殖和成熟的细胞因子。在各种中枢神经系统（CNS）损伤模型中，给予M-CSF可促进神经元存活。在此，为了诱导具有神经保护作用的小胶质细胞表型并增强运动神经元存活，从疾病发作开始，每周对突变型SOD1（G37R）转基因小鼠进行M-CSF治疗。出乎意料的是，M-CSF加速了肌萎缩侧索硬化症（ALS）的SOD1（G37R）小鼠模型中的疾病进展。接受M-CSF治疗的动物存活期缩短与肌肉神经支配减少以及小胶质细胞更易呈现巨噬细胞样表型有关，其特征是促炎细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）以及吞噬标记物CD68上调。
