Kougioumtzidou Eleni, Shimizu Takahiro, Hamilton Nicola B, Tohyama Koujiro, Sprengel Rolf, Monyer Hannah, Attwell David, Richardson William D
Wolfson Institute for Biomedical Research, University College London, London, United Kingdom.
Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom.
Elife. 2017 Jun 13;6:e28080. doi: 10.7554/eLife.28080.
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 GluA2, GluA3 and GluA4. We generated mice in which OPs lack both GluA2 and GluA3, or all three subunits GluA2/3/4, 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.
由少突胶质细胞产生的髓磷脂对于中枢神经系统中的快速信息传递至关重要。少突胶质细胞前体细胞（OPs）从轴突接收谷氨酸能突触输入，但这如何影响它们的发育尚不清楚。白质中的小鼠OPs表达AMPA受体（AMPAR）亚基GluA2、GluA3和GluA4。我们培育出了OPs同时缺乏GluA2和GluA3，或同时缺乏所有三个亚基GluA2/3/4的小鼠，这分别减少或消除了AMPAR介导的对OPs的输入。在双敲除和三敲除小鼠中，OPs的增殖和数量没有变化，但在发育过程中，皮层下白质中存活的少突胶质细胞减少了约25%。在三敲除小鼠中，这种不足持续到成年期。少突胶质细胞的缺陷导致髓鞘减少了约20%，但单个少突胶质细胞形成的髓鞘节段的平均长度、数量和厚度看起来正常。因此，来自活跃轴突的AMPAR介导的信号通过提高少突胶质细胞的存活率来刺激发育中的白质中的髓磷脂生成，而不影响髓磷脂的合成本身。
