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The role of MeCP2 in pain and its regulation by miRNAs
Dissertation   Open access

The role of MeCP2 in pain and its regulation by miRNAs

Melissa Taft Manners
Doctor of Philosophy (Ph.D.), Drexel University
Mar 2016
DOI:
https://doi.org/10.17918/etd-7156
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Abstract

Pharmacological and Toxicological Phenomena and Processes Physiological Phemonena Pharmacology Physiology
Nerve injury induces chronic pain and dysregulation of microRNAs in the dorsal root ganglia (DRG). Several downregulated microRNAs are predicted to target methyl-CpG-binding protein 2 (MeCP2) transcript. MECP2 mutations cause Rett syndrome (RTT) 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.

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