NMDA receptor signaling in oligodendrocyte progenitors is not required for oligodendrogenesis and myelination.
NMDA receptor signaling in oligodendrocyte progenitors is not required for oligodendrogenesis and myelination.
复制标题
DOI：
10.1523/jneurosci.2455-11.2011
复制
发表时间：
2011-08-31
期刊：
影响因子：
--
通讯作者：
Bergles DE
中科院分区：
文献类型：
--
作者：
De Biase LM;Kang SH;Baxi EG;Fukaya M;Pucak ML;Mishina M;Calabresi PA;Bergles DE
少突胶质细胞前体细胞（OPCs）表达NMDA受体（NMDAR），并与整个中枢神经系统（CNS）的多巴胺能神经元形成突触。虽然谷氨酸在体外影响这些祖细胞的增殖和成熟，但NMDAR信号传导在体内少突胶质细胞发生和髓鞘形成中的作用尚不清楚。在这里，我们调查的后果，基因删除的强制性NMDAR亚基NR1的OPCs和少突胶质细胞后代在中枢神经系统的发展和成熟的小鼠。NMDAR缺陷的OPCs正常增殖，在灰色和白色物质中达到适当的密度，并立即分化形成主要的白色物质束。OPCs在NMDAR信号转导缺失的情况下也保留了其特有的生理和形态学特性，并且能够与神经元轴突形成突触。然而，在NMDAR缺陷的OPCs中，钙渗透性AMPA受体的表达增强。这些结果表明，NMDAR信号不是用来控制OPC的发展，但调节周围轴突的AMPAR依赖性信号，指出这些无处不在的神经胶质细胞的额外功能。
Oligodendrocyte precursor cells (OPCs) express NMDA receptors (NMDARs) and form synapses with glutamatergic neurons throughout the central nervous system (CNS). Although glutamate influences the proliferation and maturation of these progenitors in vitro, the role of NMDAR signaling in oligodendrogenesis and myelination in vivo is not known. Here, we investigated the consequences of genetically deleting the obligatory NMDAR subunit NR1 from OPCs and their oligodendrocyte progeny in the CNS of developing and mature mice. NMDAR-deficient OPCs proliferated normally, achieved appropriate densities in gray and white matter, and differentiated to form major white matter tracts without delay. OPCs also retained their characteristic physiological and morphological properties in the absence of NMDAR signaling, and were able to form synapses with glutamatergic axons. However, expression of calcium permeable AMPA receptors was enhanced in NMDAR-deficient OPCs. These results suggest that NMDAR signaling is not used to control OPC development, but to regulate AMPAR-dependent signaling with surrounding axons, pointing to additional functions for these ubiquitous glial cells.