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

Scientific Reports, 2015 · DOI: 10.1038/srep12615 · Published: July 30, 2015

Simple Explanation

Spinal cord injury (SCI) can lead to muscle spasms. This study investigates how SCI affects mRNA editing, a process that modifies genetic information after it's transcribed from DNA. The research shows that SCI causes a decrease in the editing of mRNA for serotonin receptor 2C (5-HT2CR), which contributes to these spasms. This decrease is linked to the reduced activity of an enzyme called ADAR2. The reduction in ADAR2 activity is triggered by the body's inflammatory response to the spinal cord injury. This, in turn, alters the expression of genes in neurons, potentially leading to the restoration of neuronal excitability and muscle spasms.

Study Duration

8 weeks

Participants

16 female Sprague-Dawley rats (8 SCI, 8 control)

Evidence Level

Not specified

Key Findings

1
SCI leads to a decrease in mRNA editing of 5-HT2CR, specifically at site D, and Kv1.1 channel due to down-regulation of ADAR2 expression.
2
Genome-wide transcriptome analysis revealed two distinct components: one related to long-lasting inflammatory response and another related to post-SCI dysregulation of neurotransmission.
3
Bayesian network analysis suggests that down-regulation of ADAR2 is mostly caused by inflammatory response triggered by SCI, as well as processes related to oligodendrocyte death and demyelination.

Research Summary

This study investigates the molecular mechanisms behind post-SCI spasticity, focusing on the role of mRNA editing and ADAR2. The research demonstrates that SCI-induced inflammation leads to down-regulation of ADAR2, resulting in decreased editing of key proteins like 5-HT2CR and Kv1.1, ultimately contributing to increased neuronal excitability and muscle spasms. The findings suggest potential therapeutic targets for antispastic treatments by modulating ADAR2 activity or targeting downstream neuronal pathways.

Practical Implications

Therapeutic Targets

Modulating ADAR2 activity could offer new avenues for antispastic drug therapy.

Broader CNS Implications

The link between ADAR2, inflammation, and neuronal excitability may extend to other neurological disorders with spasticity, such as multiple sclerosis.

Personalized Medicine

Understanding the specific molecular pathways involved in ADAR2 regulation could allow for more targeted and personalized treatments for SCI-induced spasticity.

Study Limitations

1
The study is limited to a rat model of SCI, and findings may not directly translate to humans.
2
The study focuses on a specific time point (8 weeks post-SCI), and the long-term effects of ADAR2 down-regulation remain unclear.
3
The precise cellular mechanisms by which inflammation triggers ADAR2 down-regulation require further investigation.

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