Origin and distribution of bone marrow-derived cells in the central nervous system in a mouse model of amyotrophic lateral sclerosis
Origin and distribution of bone marrow-derived cells in the central nervous system in a mouse model of amyotrophic lateral sclerosis
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DOI：
10.1002/glia.20331
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发表时间：
2006-05-01
期刊：
影响因子：
6.2
通讯作者：
Krieger, C
中科院分区：
文献类型：
--
作者：
Solomon, JN;Lewis, CAB;Krieger, C
肌萎缩侧索硬化症(ALS)与中枢神经系统(CNS)内小胶质细胞数量的增加有关。然而，目前尚不清楚小胶质细胞增生症是由于中枢神经系统驻留的小胶质细胞的增殖，还是骨髓来源的小胶质细胞前体的募集所致。在这里，我们通过将绿色荧光蛋白(GFP)标记的BM细胞移植到过表达人突变超氧化物歧化酶1(MSOD)的骨髓切除小鼠(ALS的小鼠模型)中，评估了骨髓来源细胞在脊髓中的分布和数量。GFP+BM移植不影响mSOD小鼠的疾病进展率。对照组小鼠脊髓内小胶质细胞和GFP+细胞的平均数量与无症状小鼠相比差异无统计学意义，也没有随年龄的变化而变化。当mSOD小鼠出现疾病症状时，脊髓内的GFP+细胞和MicroghA(F4/80+和CD11b+细胞)数量比年龄匹配的对照组增加，一直持续到疾病末期。虽然我们观察到有疾病症状的mSOD小鼠脊髓中GFP+细胞的数量增加，但GFP+F4/80+细胞的平均数量不到所有F4/80+细胞的20%，并且不随疾病的进展而增加。此外，CD45+GFP-和CD45+GFP+细胞的相对增殖率具有可比性。因此，我们证明mSOD小鼠脊髓组织中出现的小胶质细胞增多症主要是由于驻留的小胶质细胞的扩张，而不是由于小胶质细胞前体从循环中招募。(C)2006年Wiley-Liss，Inc.
Amyotrophic lateral sclerosis (ALS) is associated with increased numbers of microglia within the central nervous system (CNS). However, it is unknown whether the microgliosis results from proliferation of CNS resident microglia, or recruitment of bone marrow (BM)-derived microglial precursors. Here we assess the distribution and number of BM-derived cells in spinal cord using transplantation of green fluorescent protein (GFP)-labeled BM cells into myelo-ablated mice over-expressing human mutant superoxide dismutase 1 (mSOD), a murine model of ALS. Transplantation of GFP+ BM did not affect the rate of disease progression in mSOD mice. Mean numbers of microglia and GFP+ cells in spinal cords of control mice were not significantly different from those in asymptomatic mSOD mice and showed no change with animal age. The number of GFP+ cells and microgha (F4/80+ and CD11b+ cells) within the spinal cord of mSOD mice increased compared to age-matched controls at a time when mSOD mice exhibited disease symptoms, continuing up to disease end-stage. Although we observed an increase in the number of GFP+ cells in spinal cords of mSOD mice with disease symptoms, mean numbers of GFP+ F4/80+ cells comprised less than 20% of all F4/80+ cells and did not increase with disease progression. Furthermore, the relative rates of proliferation in CD45+GFP- and CD45+GFP+ cells were comparable. Thus, we demonstrate that the microgliosis present in spinal cord tissue of mSOD mice is primarily due to an expansion of resident microglia and not to the recruitment of microglial precursors from the circulation. (c) 2006 Wiley-Liss,Inc.