Selective reduction in microglia density and function in the white matter of colony-stimulating factor-1-deficient mice.
Selective reduction in microglia density and function in the white matter of colony-stimulating factor-1-deficient mice.
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DOI：
10.1002/jnr.22096
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发表时间：
2009-09
影响因子：
4.2
通讯作者：
Duncan ID
中科院分区：
文献类型：
--
作者：
Kondo Y;Duncan ID
小胶质细胞在多发性硬化症和脑白质营养不良等髓鞘质疾病以及中枢神经系统的其他病理状况中是否发挥有益或有害的作用仍然存在争议。由于集落刺激因子 1 基因的失活突变，骨石症 (op/op) 小鼠的单核细胞谱系细胞数量减少。为了确定这种突变小鼠是否可用于研究小胶质细胞在髓鞘质疾病中的作用，我们量化了 op/op 小鼠中枢神经系统中小胶质细胞的数量，并探索了它们对刺伤造成的脑损伤做出反应的能力。与-ge匹配的野生型对照相比，2个月大的op/op小鼠的白质束中的小胶质细胞密度显着降低（胼胝体中降低63.6%，脊髓背柱中降低86.4%），而灰质、大脑皮层中的降低幅度较小（24.0%）。 7 个月大时也出现了类似的下降。脊髓髓鞘形成的形态测量研究表明，op/op 小鼠的髓鞘发育不受影响。针对刺伤，op/op 小鼠中小胶质细胞/巨噬细胞数量的增加明显低于野生型对照。这些发现表明，该突变体是研究小胶质细胞/巨噬细胞在髓鞘质疾病病理生理学中的作用的有价值的模型。
It is still debated whether microglia play a beneficial or harmful role in myelin disorders such as multiple sclerosis and leukodystrophies as well as in other pathological conditions of the central nervous system. The osteopetrotic (op/op) mouse has reduced numbers of cells of monocyte lineage as a result of an inactivating mutation in the colony stimulating factor-1 gene. To determine whether this mutant mouse might be used to study the role of microglia in myelin disorders, we quantified the number of microglia in the central nervous system of op/op mice and explored their ability to respond to brain injury created by a stab wound. Microglial density in the 2-month-old op/op mice was significantly decreased in the white matter tracts compared with the -ge matched wild-type controls (by 63.6% in the corpus callosum and 86.4% in the spinal dorsal column), whereas the decrease was less in the gray matter, cerebral cortex (24.0%). A similar decrease was seen at 7 months of age. Morphometric studies of spinal cord myelination showed that development of myelin was not affected in op/op mice. In response to a stab wound, the increase in the number of microglia/macrophages in op/op mice was significantly less pronounced than that in wild-type control. These findings demonstrate that this mutant is a valuable model in which to study roles of microglia/macrophages in the pathophysiology of myelin disorders.