Signalling through AMPA receptors on oligodendrocyte precursors promotes myelination by enhancing oligodendrocyte survival
Signalling through AMPA receptors on oligodendrocyte precursors promotes myelination by enhancing oligodendrocyte survival
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DOI：
10.7554/elife.28080
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发表时间：
2017-06-13
期刊：
影响因子：
7.7
通讯作者：
Richardson, William D.
中科院分区：
文献类型：
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作者：
Kougioumtzidou, Eleni;Shimizu, Takahiro;Richardson, William D.
髓鞘是由少突胶质细胞制造的，对中枢神经系统的快速信息传递是必不可少的。少突胶质前体细胞(OPs)从轴突接受谷氨酸能突触输入，但这如何影响它们的发育尚不清楚。小鼠白质OPs表达AMPA受体(AMPAR)亚单位GIuA2、GIuA3和GIuA4。我们产生了OPs缺乏GIuA2和GIuA3或全部三个亚单位GIuA2/3/4的小鼠，这三个亚基分别减少或取消了AMPAR介导的OPs输入。在两次和三次敲除中，OP的增殖和数量都没有变化，但在发育过程中，皮质下白质中存活的少突胶质细胞减少了25%。在三次淘汰赛中，这种差距一直持续到成年。少突胶质细胞缺失导致髓鞘减少20%，但单个少突胶质细胞形成的髓鞘节间的平均长度、数目和厚度均正常。因此，AMPAR介导的来自活跃轴突的信号通过提高少突胶质细胞的存活来刺激发育中的白质中髓鞘的产生，而不影响髓鞘合成本身。
Myelin, made by oligodendrocytes, is essential for rapid information transfer in the central nervous system. Oligodendrocyte precursors (OPs) receive glutamatergic synaptic input from axons but how this affects their development is unclear. Murine OPs in white matter express AMPA receptor (AMPAR) subunits GIuA2, GIuA3 and GIuA4. We generated mice in which OPs lack both GIuA2 and GIuA3, or all three subunits GIuA2/3/4, which respectively reduced or abolished AMPAR-mediated input to OPs. In both double- and triple-knockouts OP proliferation and number were unchanged but 25% fewer oligodendrocytes survived in the subcortical white matter during development. In triple knockouts, this shortfall persisted into adulthood. The oligodendrocyte deficit resulted in 20% fewer myelin sheaths but the average length, number and thickness of myelin internodes made by individual oligodendrocytes appeared normal. Thus, AMPAR-mediated signalling from active axons stimulates myelin production in developing white matter by enhancing oligodendrocyte survival, without influencing myelin synthesis per se.