Manners Melissa T, Tian Yuzhen, Zhou Zhaolan, Ajit Seena K
Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, USA.
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, USA.
FEBS Open Bio. 2015 Aug 31;5:733-40. doi: 10.1016/j.fob.2015.08.010. eCollection 2015.
Nerve injury induces chronic pain and dysregulation of microRNAs in dorsal root ganglia (DRG). Several downregulated microRNAs are predicted to target Mecp2. MECP2 mutations cause Rett syndrome and these patients report decreased pain perception. We confirmed MeCP2 upregulation in DRG following nerve injury and repression of MeCP2 by miRNAs in vitro. MeCP2 regulates brain-derived neurotrophic factor (BDNF) and downregulation of MeCP2 by microRNAs decreased Bdnf in vitro. MeCP2 T158A mice exhibited reduced mechanical sensitivity and Mecp2-null and MeCP2 T158A mice have decreased Bdnf in DRG. MeCP2-mediated regulation of Bdnf in the DRG could contribute to altered pain sensitivity.
神经损伤会引发慢性疼痛以及背根神经节（DRG）中微小RNA的失调。预测有几种下调的微小RNA靶向Mecp2。MECP2突变会导致雷特综合征，这些患者表现出疼痛感知下降。我们证实了神经损伤后DRG中MeCP2上调，以及体外微小RNA对MeCP2的抑制作用。MeCP2调节脑源性神经营养因子（BDNF），微小RNA对MeCP2的下调在体外降低了Bdnf。MeCP2 T158A小鼠表现出机械敏感性降低，Mecp2基因敲除小鼠和MeCP2 T158A小鼠的DRG中Bdnf减少。MeCP2在DRG中介导的对Bdnf的调节可能导致疼痛敏感性改变。
