摘要：“Rett’s综合症”是由于MeCP2功能丧失而引起的一种疾病，各类自闭症的神经症状都与此有关。虽然“Rett’s综合症”中神经系统失常的根本原因是神经元的损伤，但1个小鼠模型的实验表明，胶质细胞中（主要是星形细胞）MeCP2表达的遗传校正，可以逆转这种神经疾病中3个标志性的异常行为。神经形态及神经传递标记也得以恢复，表明在“Rett’s综合症”发病过程中，胶质细胞和神经细胞之间有1个互动机制。
生物探索推荐英文论文摘要：
Nature 475, 497–500 (28 July 2011)
Doi:10.1038/nature10214
A role for glia in the progression of Rett’s syndrome
Abstract:
Rett’s syndrome (RTT) is an X-chromosome-linked autism spectrum disorder caused by loss of function of the transcription factor methyl-CpG-binding protein 2 (MeCP2). Although MeCP is expressed in most tissues2, loss of MeCP2 expression results primarily in neurological symptoms1, . Earlier studies suggested the idea that RTT is due exclusively to loss of MeCP2 function in neurons. Although defective neurons clearly underlie the aberrant behaviours, we and others showed recently that the loss of MECP2 from glia negatively influences neurons in a non-cell-autonomous fashion. Here we show that in globally MeCP2-deficient mice, re-expression of Mecp2 preferentially in astrocytes significantly improved locomotion and anxiety levels, restored respiratory abnormalities to a normal pattern, and greatly prolonged lifespan compared to globally null mice. Furthermore, restoration of MeCP2 in the mutant astrocytes exerted a non-cell-autonomous positive effect on mutant neurons in vivo, restoring normal dendritic morphology and increasing levels of the excitatory glutamate transporter VGLUT1. Our study shows that glia, like neurons, are integral components of the neuropathology of RTT, and supports the targeting of glia as a strategy for improving the associated symptoms.
Figure 1: MeCP2 is restored specifically in GFAP+ astrocytes of TAM-treated Mecp2Stop/y-hGFAPcreT2 mice.
