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Decrease of mRNA Editing after Spinal Cord Injury is Caused by Down-regulation of ADAR2 that is Triggered by Inflammatory Response.

Abstract：

:We recently showed that spinal cord injury (SCI) leads to a decrease in mRNA editing of serotonin receptor 2C (5-HT2CR) contributing to post-SCI spasticity. Here we study post-SCI mRNA editing and global gene expression using massively parallel sequencing. Evidence is presented that the decrease in 5-HT2CR editing is caused by down-regulation of adenosine deaminase ADAR2 and that editing of at least one other ADAR2 target, potassium channel Kv1.1, is decreased after SCI. Bayesian network analysis of genome-wide transcriptome data indicates that down-regulation of ADAR2 (1) is triggered by persistent inflammatory response to SCI that is associated with activation of microglia and (2) results in changes in neuronal gene expression that are likely to contribute both to post-SCI restoration of neuronal excitability and muscle spasms. These findings have broad implications for other diseases of the Central Nervous System and could open new avenues for developing efficacious antispastic treatments.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Di Narzo AF,Kozlenkov A,Ge Y,Zhang B,Sanelli L,May Z,Li Y,Fouad K,Cardozo C,Koonin EV,Bennett DJ,Dracheva S

doi

10.1038/srep12615

subject

Has Abstract

pub_date

2015-07-30 00:00:00

pages

12615

issn

2045-2322

pii

srep12615

journal_volume

5

pub_type

杂志文章

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