Vollum Institute, Oregon Health & Science University, Portland, United States.
Elife. 2018 Jan 9;7:e31629. doi: 10.7554/eLife.31629.
Studies linking mutations in Methyl CpG Binding Protein 2 (MeCP2) to physiological defects in the neurological disease, Rett syndrome, have focused largely upon neuronal dysfunction despite MeCP2 ubiquitous expression. Here we explore roles for astrocytes in neuronal network function using cortical slice recordings. We find that astrocyte stimulation in wild-type mice increases excitatory synaptic activity that is absent in male mice lacking MeCP2 globally. To determine the cellular basis of the defect, we exploit a female mouse model for Rett syndrome that expresses wild-type MeCP2-GFP in a mosaic distribution throughout the brain, allowing us to test all combinations of wild-type and mutant cells. We find that the defect is dependent upon MeCP2 expression status in the astrocytes and not in the neurons. Our findings highlight a new role for astrocytes in regulation of excitatory synaptic signaling and in the neurological defects associated with Rett syndrome.
研究将 Methyl CpG Binding Protein 2（MeCP2）突变与神经疾病雷特综合征的生理缺陷联系起来，尽管 MeCP2 广泛表达，但主要集中在神经元功能障碍上。在这里，我们使用皮质切片记录来探索星形胶质细胞在神经元网络功能中的作用。我们发现，在野生型小鼠中刺激星形胶质细胞会增加兴奋性突触活动，而在缺乏全局 MeCP2 的雄性小鼠中则不存在这种活动。为了确定缺陷的细胞基础，我们利用一种雷特综合征的雌性小鼠模型，该模型在大脑中以镶嵌分布表达野生型 MeCP2-GFP，使我们能够测试野生型和突变细胞的所有组合。我们发现，缺陷取决于星形胶质细胞中 MeCP2 的表达状态，而不是神经元。我们的研究结果强调了星形胶质细胞在调节兴奋性突触信号和与雷特综合征相关的神经缺陷中的新作用。
