Aw Sherry Shiying, Lim Isaac Kok Hwee, Tang Melissa Xue Mei, Cohen Stephen Michael
Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore.
Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore.
Cell Rep. 2017 May 30;19(9):1783-1793. doi: 10.1016/j.celrep.2017.05.010.
Glutamate is a ubiquitous neurotransmitter, mediating information flow between neurons. Defects in the regulation of glutamatergic transmission can result in glutamate toxicity, which is associated with neurodegeneration. Interestingly, glutamate receptors are expressed in glia, but little is known about their function, and the effects of their misregulation, in these non-neuronal cells. Here, we report a glio-protective role for Drosophila mir-263a mediated by its regulation of glutamate receptor levels in glia. mir-263a mutants exhibit a pronounced movement defect due to aberrant overexpression of CG5621/Grik, Nmdar1, and Nmdar2. mir-263a mutants exhibit excitotoxic death of a subset of astrocyte-like and ensheathing glia in the CNS. Glial-specific normalization of glutamate receptor levels restores cell numbers and suppresses the movement defect. Therefore, microRNA-mediated regulation of glutamate receptor levels protects glia from excitotoxicity, ensuring CNS health. Chronic low-level glutamate receptor overexpression due to mutations affecting microRNA (miRNA) regulation might contribute to glial dysfunction and CNS impairment.
谷氨酸是一种广泛存在的神经递质，介导神经元之间的信息流。谷氨酸能传递调节缺陷可导致谷氨酸毒性，这与神经退行性变有关。有趣的是，谷氨酸受体在胶质细胞中表达，但对于它们在这些非神经元细胞中的功能以及调控异常的影响却知之甚少。在这里，我们报告果蝇mir-263a通过调节胶质细胞中谷氨酸受体水平发挥神经胶质保护作用。mir-263a突变体由于CG5621/Grik、Nmdar1和Nmdar2的异常过表达而表现出明显的运动缺陷。mir-263a突变体在中枢神经系统中表现出一部分星形胶质细胞样和包被胶质细胞的兴奋性毒性死亡。谷氨酸受体水平的胶质细胞特异性正常化可恢复细胞数量并抑制运动缺陷。因此，微小RNA介导的谷氨酸受体水平调节可保护胶质细胞免受兴奋性毒性，确保中枢神经系统健康。由于影响微小RNA（miRNA）调节的突变导致的慢性低水平谷氨酸受体过表达可能导致胶质细胞功能障碍和中枢神经系统损伤。
