The role of microglia in brain maintenance: implications for Rett syndrome.
The role of microglia in brain maintenance: implications for Rett syndrome.
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DOI：
10.1016/j.it.2012.10.002
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发表时间：
2013-03
影响因子：
16.8
通讯作者：
Kipnis J
中科院分区：
文献类型：
--
作者：
Derecki NC;Cronk JC;Kipnis J
小胶质细胞在中枢神经系统病理学中的作用已被广泛研究，最近，对健康大脑中小胶质细胞的检查已经对其许多功能产生了重要的见解。长期以来，人们认为小胶质细胞基本上是“静止”的细胞，除非被激活，这被认为是疾病的标志。然而，最近越来越清楚的是，它们是非常动态的细胞，不断地对环境进行采样，并适应微妙的刺激。沿着这些路线，我们的实验室已经确定了一个新的和意想不到的作用，小胶质细胞吞噬-或缺乏-在Rett综合征的病理生理学，一种神经发育疾病引起的基因突变编码甲基CpG结合蛋白（MECP）2。也就是说，我们发现野生型Mecp 2在Mecp 2缺失小鼠的骨髓细胞中的特异性表达足以阻止与这种毁灭性疾病相关的主要症状。然而，如果小胶质细胞的吞噬活性受到抑制，这种有益的作用就会消失。在这里，我们将讨论小胶质细胞的起源、小胶质细胞在大脑发育和维持中的作用以及成人大脑中骨髓祖细胞增加小胶质细胞的现象。最后，我们将详细讨论小胶质细胞作为Rett综合征和其他神经系统疾病临床靶点的有益作用。
The role of microglia in central nervous system pathology has been studied extensively, and more recently, examination of microglia in the healthy brain has yielded important insights into their many functions. It was long assumed that microglia were essentially “quiescent” cells, unless provoked into activation, which was considered a hallmark of disease. More recently, however, it has become increasingly clear that they are extraordinarily dynamic cells, constantly sampling their environment and adjusting to exquisitely delicate stimuli. Along these lines, our lab has identified a new and unexpected role for microglial phagocytosis—or lack thereof—in the pathophysiology of Rett syndrome, a neurodevelopmental disease caused by mutation of the gene encoding methyl-CpG binding protein (MECP)2. Namely, we showed that specific expression of wild-type Mecp2 in myeloid cells of Mecp2-null mice is sufficient to arrest major symptoms associated with this devastating disease. This beneficial effect, however, is abolished if phagocytic activity of microglia is inhibited. Here, we will discuss microglial origins, the role of microglia in brain development and maintenance, and the phenomenon of microglial augmentation by myeloid progenitor cells in the adult brain. Finally, we will address in some detail the beneficial roles of microglia as clinical targets in Rett syndrome and other neurological disorders.
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影响因子：
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