2012年10月17日 訊 /生物谷BIOON/ --在神經(jīng)系統(tǒng)許多病變中，通常會(huì)發(fā)生這樣一種事件-小神經(jīng)膠質(zhì)細(xì)胞（Microglia）會(huì)被激活,，從神經(jīng)系統(tǒng)監(jiān)督者的角色轉(zhuǎn)變?yōu)?ldquo;好戰(zhàn)分子”,。 小神經(jīng)膠質(zhì)細(xì)胞是機(jī)體神經(jīng)系統(tǒng)的免疫細(xì)胞，其可以攝取并且破壞致病及損傷的神經(jīng)細(xì)胞,。截止目前,，關(guān)于其在機(jī)體被激活的過程或分子機(jī)制,，研究者并不清楚,。如今，來自麥吉爾大學(xué)等處的研究者通過研究揭示了這種分子機(jī)制,，小神經(jīng)膠質(zhì)細(xì)胞可以被Runx1基因調(diào)節(jié)來控制其作為監(jiān)督者和處于被激活狀態(tài)（好戰(zhàn)分子）之間的平衡,。相關(guān)研究成果刊登于國(guó)際雜志Journal of Neuroscience上。
作為監(jiān)督者的角色,，小神經(jīng)膠質(zhì)細(xì)胞需要等待神經(jīng)系統(tǒng)中錯(cuò)誤發(fā)生才能實(shí)施保護(hù)的角色，其包括小的細(xì)胞體和較長(zhǎng)的細(xì)胞分枝,，長(zhǎng)的分枝可以感知其周圍環(huán)境,。一旦神經(jīng)系統(tǒng)出現(xiàn)損傷，小神經(jīng)膠質(zhì)細(xì)胞就會(huì)被激活變成好戰(zhàn)分子,，來消滅侵入機(jī)體的外界病原物質(zhì),，如病毒、細(xì)菌以及各種神經(jīng)細(xì)胞的損傷。
研究者發(fā)現(xiàn)小神經(jīng)膠質(zhì)細(xì)胞在成人大腦中的激活過程實(shí)際上就是神經(jīng)系統(tǒng)發(fā)育的一個(gè)重演,，在發(fā)育的大腦中,，小神經(jīng)膠質(zhì)細(xì)胞處于其早期戰(zhàn)斗形式，并且有足夠能力來清除細(xì)胞碎片和冗余的神經(jīng)系統(tǒng)連接,。當(dāng)小神經(jīng)膠質(zhì)細(xì)胞生成后如果處于被激活狀態(tài)就會(huì)扮演監(jiān)督者的角色,，在這種狀態(tài)下，其會(huì)維持其監(jiān)督的職責(zé)直到機(jī)體神經(jīng)系統(tǒng)受到損傷后,，才能被激活來保護(hù)機(jī)體神經(jīng)系統(tǒng),。
研究者Stefano說，我們的研究揭示了特異性基因Runx1的重要作用,，其可以促進(jìn)小神經(jīng)膠質(zhì)細(xì)胞從早期激活狀態(tài)變成處于監(jiān)督者的狀態(tài)，我們的研究表明,，Runx1在早期激活狀態(tài)的小神經(jīng)膠質(zhì)細(xì)胞中進(jìn)行表達(dá),，如果細(xì)胞中Runx1的功能被抑制，那么膠質(zhì)細(xì)胞就會(huì)長(zhǎng)期維持激活狀態(tài),，這樣其轉(zhuǎn)化為監(jiān)督者角色的時(shí)間就會(huì)被耽誤,。對(duì)小鼠進(jìn)行研究發(fā)現(xiàn)，當(dāng)小鼠神經(jīng)系統(tǒng)受到損傷,，小神經(jīng)膠質(zhì)細(xì)胞中的Runx1的表達(dá)就會(huì)被誘導(dǎo),，這也揭示了Runx1或許在控制“好戰(zhàn)分子”小神經(jīng)膠質(zhì)細(xì)胞如何維持其在神經(jīng)系統(tǒng)中處于激活狀態(tài)扮演著重要作用。
這項(xiàng)研究改變了研究者對(duì)于發(fā)育和損傷大腦中的膠質(zhì)細(xì)胞生物學(xué)的理解,，這或許為將來相關(guān)的神經(jīng)病理疾病的治療帶來幫助,。未來制藥公司或許會(huì)以小神經(jīng)膠質(zhì)細(xì)胞激活的調(diào)節(jié)為靶點(diǎn)來開發(fā)出新型的治療神經(jīng)系統(tǒng)疾病的藥物。（生物谷Bioon.com）
編譯自：Attack! Silent Watchmen Charge to Defend the Nervous System
doi:10.1523/JNEUROSCI.6182-11.2012
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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..
