The Pathophysiological Role of Microglia in Dynamic Surveillance, Phagocytosis and Structural Remodeling of the Developing CNS.
The Pathophysiological Role of Microglia in Dynamic Surveillance, Phagocytosis and Structural Remodeling of the Developing CNS.
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DOI：
10.3389/fnmol.2017.00191
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发表时间：
2017
影响因子：
4.8
通讯作者：
Donato R
中科院分区：
文献类型：
--
作者：
Arcuri C;Mecca C;Bianchi R;Giambanco I;Donato R
在脊椎动物中，在胚胎日E7.0和E9.0之间的卵黄囊中的早期造血波期间，中胚层小叶的巨噬细胞谱系的细胞进入发育中的中枢神经系统（CNS）并起源于发育中的天然小胶质细胞。根据物种的不同，小胶质细胞占成人大脑中神经胶质细胞的5-20%。在这里，我们简要讨论了小胶质细胞的一些典型功能，即，细胞因子分泌和从M1到M2表型的功能转变。此外，我们还回顾了小胶质细胞的非典型功能，如调节吞噬作用，突触修剪，塑造出生后的神经回路的研究。在后一种情况下，小胶质细胞对一些神经发育障碍的贡献现在已经得到了很好的证实。Nasu-Hakola（NHD）病被认为是一种原发性小胶质细胞病，伴有髓样细胞2（TREM-2）信号转导上表达的DNAX活化蛋白12（DAP 12）-触发受体的改变以及大分子和凋亡细胞的去除，随后是继发性小胶质细胞活化。在Rett综合征中，Mecp 2-/-小胶质细胞显示出吞噬能力的实质性损害，尽管小胶质细胞的作用尚不清楚。在Tourette综合征（TS）的小鼠模型中，也描述了小胶质细胞异常，并且缺乏小胶质细胞介导的神经保护是明显的。在这里，我们回顾了小胶质细胞在无炎症的神经发育障碍中的作用，以及小胶质细胞在中枢神经系统发育中的复杂作用。
In vertebrates, during an early wave of hematopoiesis in the yolk sac between embryonic day E7.0 and E9.0, cells of mesodermal leaflet addressed to macrophage lineage enter in developing central nervous system (CNS) and originate the developing native microglial cells. Depending on the species, microglial cells represent 5–20% of glial cells resident in adult brain. Here, we briefly discuss some canonical functions of the microglia, i.e., cytokine secretion and functional transition from M1 to M2 phenotype. In addition, we review studies on the non-canonical functions of microglia such as regulation of phagocytosis, synaptic pruning, and sculpting postnatal neural circuits. In this latter context the contribution of microglia to some neurodevelopmental disorders is now well established. Nasu-Hakola (NHD) disease is considered a primary microgliopathy with alterations of the DNAX activation protein 12 (DAP12)-Triggering receptor expressed on myeloid cells 2 (TREM-2) signaling and removal of macromolecules and apoptotic cells followed by secondary microglia activation. In Rett syndrome Mecp2-/- microglia shows a substantial impairment of phagocytic ability, although the role of microglia is not yet clear. In a mouse model of Tourette syndrome (TS), microglia abnormalities have also been described, and deficient microglia-mediated neuroprotection is obvious. Here we review the role of microglial cells in neurodevelopmental disorders without inflammation and on the complex role of microglia in developing CNS.