MicroRNAs downregulated in neuropathic pain regulate MeCP2 and BDNF related to pain sensitivity

被引:32
|
作者
Manners, Melissa T. [1 ]
Tian, Yuzhen [1 ]
Zhou, Zhaolan [2 ]
Ajit, Seena K. [1 ]
机构
[1] Drexel Univ, Pharmacol & Physiol, Coll Med, Philadelphia, PA 19102 USA
[2] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA
来源
FEBS OPEN BIO | 2015年 / 5卷
关键词
MeCP2; miRNA; Neuropathic pain; BDNF; CPG-BINDING PROTEIN-2; DORSAL-ROOT GANGLIA; CHRONIC CONSTRICTION INJURY; RETT-SYNDROME; NEUROTROPHIC FACTOR; NERVE INJURY; EPIGENETIC REGULATION; NEUROLOGICAL DISEASE; EXPERIMENTAL-MODELS; INFLAMMATORY PAIN;
D O I
10.1016/j.fob.2015.08.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2015 The Authors. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
引用
收藏
页码:733 / 740
页数:8
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