2012年10月17日 讯 /生物谷BIOON/ --在神经系统许多病变中，通常会发生这样一种事件-小神经胶质细胞（Microglia）会被激活，从神经系统监督者的角色转变为“好战分子”。 小神经胶质细胞是机体神经系统的免疫细胞，其可以摄取并且破坏致病及损伤的神经细胞。截止目前，关于其在机体被激活的过程或分子机制，研究者并不清楚。如今，来自麦吉尔大学等处的研究者通过研究揭示了这种分子机制，小神经胶质细胞可以被Runx1基因调节来控制其作为监督者和处于被激活状态（好战分子）之间的平衡。相关研究成果刊登于国际杂志Journal of Neuroscience上。
作为监督者的角色，小神经胶质细胞需要等待神经系统中错误发生才能实施保护的角色，其包括小的细胞体和较长的细胞分枝，长的分枝可以感知其周围环境。一旦神经系统出现损伤，小神经胶质细胞就会被激活变成好战分子，来消灭侵入机体的外界病原物质，如病毒、细菌以及各种神经细胞的损伤。
研究者发现小神经胶质细胞在成人大脑中的激活过程实际上就是神经系统发育的一个重演，在发育的大脑中，小神经胶质细胞处于其早期战斗形式，并且有足够能力来清除细胞碎片和冗余的神经系统连接。当小神经胶质细胞生成后如果处于被激活状态就会扮演监督者的角色，在这种状态下，其会维持其监督的职责直到机体神经系统受到损伤后，才能被激活来保护机体神经系统。
研究者Stefano说，我们的研究揭示了特异性基因Runx1的重要作用，其可以促进小神经胶质细胞从早期激活状态变成处于监督者的状态，我们的研究表明，Runx1在早期激活状态的小神经胶质细胞中进行表达，如果细胞中Runx1的功能被抑制，那么胶质细胞就会长期维持激活状态，这样其转化为监督者角色的时间就会被耽误。对小鼠进行研究发现，当小鼠神经系统受到损伤，小神经胶质细胞中的Runx1的表达就会被诱导，这也揭示了Runx1或许在控制“好战分子”小神经胶质细胞如何维持其在神经系统中处于激活状态扮演着重要作用。
这项研究改变了研究者对于发育和损伤大脑中的胶质细胞生物学的理解，这或许为将来相关的神经病理疾病的治疗带来帮助。未来制药公司或许会以小神经胶质细胞激活的调节为靶点来开发出新型的治疗神经系统疾病的药物。（生物谷Bioon.com）
编译自：Attack! Silent Watchmen Charge to Defend the Nervous System
doi:10.1523/JNEUROSCI.6182-11.2012
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PMID:
Regulation of Postnatal Forebrain Amoeboid Microglial Cell Proliferation and Development by the Transcription Factor Runx1
Morena Zusso1,3, Laurent Methot1, Rita Lo1, Andrew D. Greenhalgh2, Samuel David2, and Stefano Stifani1
Microglia are the immune cells of the nervous system, where they act as resident macrophages during inflammatory events underlying many neuropathological conditions. Microglia derive from primitive myeloid precursors that colonize the nervous system during embryonic development. In the postnatal brain, microglia are initially mitotic, rounded in shape (amoeboid), and phagocytically active. As brain development proceeds, they gradually undergo a transition to a surveillant nonphagocytic state characterized by a highly branched (ramified) morphology. This ramification process is almost recapitulated in reverse during the process of microglia activation in the adult brain, when surveillant microglia undergo a ramified-to-amoeboid morphological transformation and become phagocytic in response to injury or disease. Little is known about the mechanisms controlling amoeboid microglial cell proliferation, activation, and ramification during brain development, despite the critical role of these processes in the establishment of the adult microglia pool and their relevance to microglia activation in the adult brain. Here we show that the mouse transcription factor Runx1, a key regulator of myeloid cell proliferation and differentiation, is expressed in forebrain amoeboid microglia during the first two postnatal weeks. Runx1 expression is then downregulated in ramified microglia. Runx1 inhibits mouse amoeboid microglia proliferation and promotes progression to the ramified state. We show further that Runx1 expression is upregulated in microglia following nerve injury in the adult mouse nervous system. These findings provide insight into the regulation of postnatal microglia activation and maturation to the ramified state and have implications for microglia biology in the developing and injured brain..
