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  4. miR-434-3p and DNA hypomethylation co-regulate eIF5A1 to increase AChRs and to improve plasticity in SCT rat skeletal muscle

miR-434-3p and DNA hypomethylation co-regulate eIF5A1 to increase AChRs and to improve plasticity in SCT rat skeletal muscle

Scientific Reports, 2016 · DOI: 10.1038/srep22884 · Published: March 11, 2016

Spinal Cord InjuryNeurologyGenetics

Simple Explanation

This study investigates the role of microRNAs (miRNAs) in modulating acetylcholine receptors (AChRs) after spinal cord transection (SCT) in rats. It identifies miR-434-3p as a key regulator of eIF5A1 expression, which in turn influences AChRs expression and locomotor function. The research demonstrates that miR-434-3p negatively regulates eIF5A1, and its depletion in SCT rat skeletal muscle leads to increased AChRs numbers and improved function scores. Conversely, overexpression of miR-434-3p reduces AChRs expression and impairs motor function recovery. Additionally, the study reveals that DNA demethylation also up-regulates eIF5A1 after SCT, suggesting a co-regulatory mechanism involving both miR-434-3p and DNA methylation in the recovery of locomotor function after SCI.

Study Duration
35 dpo
Participants
Adult female Sprague-Dawley rats weighing 200–250 g
Evidence Level
Not specified

Key Findings

  • 1
    miR-434-3p directly targets eIF5A1 to negatively regulate its expression in rat skeletal muscle.
  • 2
    Down-regulation of miR-434-3p after SCT leads to increased eIF5A1 expression, which promotes AChRs formation and improves locomotor function.
  • 3
    DNA hypomethylation contributes to the up-regulation of eIF5A1 expression in hindlimb muscles after SCT.

Research Summary

This study elucidates the role of miR-434-3p in regulating eIF5A1 expression and AChRs formation in a rat model of spinal cord transection (SCT). The findings demonstrate that miR-434-3p acts as a negative regulator of eIF5A1, and its down-regulation after SCT contributes to increased AChRs numbers and improved locomotor function. The research identifies DNA hypomethylation as an additional mechanism that up-regulates eIF5A1 expression after SCT, suggesting a complex interplay between microRNA regulation and epigenetic modification in the recovery process. The study suggests that targeting miR-434-3p in skeletal muscle could be a potential therapeutic strategy for promoting functional recovery after spinal cord injury.

Practical Implications

Therapeutic Target Identification

miR-434-3p and eIF5A1 as potential therapeutic targets for SCI.

Biomarker Development

miR-434-3p expression levels as a biomarker for monitoring recovery after SCI.

Personalized Medicine

Tailoring treatment strategies based on individual miR-434-3p expression profiles.

Study Limitations

  • 1
    Study limited to rat model
  • 2
    Focus primarily on GS muscle
  • 3
    Long-term effects not assessed

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