MicroRNAs 21 and 199a-3p Regulate Axon Growth Potential through Modulation of Pten and mTor mRNAs

eNeuro, 2021 · DOI: https://doi.org/10.1523/ENEURO.0155-21.2021 · Published: July 29, 2021

Regenerative Medicine Neurology Genetics

Simple Explanation

This study investigates how microRNAs (miRs), specifically miR-21 and miR-199a-3p, influence axon growth by regulating PTEN and mTOR, which are important for protein synthesis in neurons. The research shows that miR-21 promotes axon growth while miR-199a-3p inhibits it. They achieve this by controlling the levels of PTEN and mTOR, respectively, which in turn affects protein synthesis crucial for axon regeneration. The findings suggest that manipulating miR-21 and miR-199a-3p levels could be a potential strategy to enhance axon regeneration after nervous system injuries, as these miRs can modify the neuron's ability to translate regeneration-associated genes.

Study Duration

Not specified

Participants

Male Sprague Dawley rats (175–250 g) and Embryonic day (E)18 male and female rat pups

Evidence Level

Not specified

Key Findings

1
miR-21 increases and miR-199a-3p decreases in DRG neurons after in vivo axotomy, suggesting injury-induced changes in these miRs.
2
miR-21 directly binds to Pten mRNA, decreasing Pten levels, while miR-199a-3p directly binds to mTor mRNA, reducing mTor levels.
3
Overexpression of miR-21 increases overall and intra-axonal protein synthesis, whereas miR-199a-3p overexpression decreases protein synthesis.

Research Summary

The study demonstrates that miR-21 and miR-199a-3p regulate axon growth by modulating the PTEN/mTOR pathway, which affects protein synthesis in neurons. Injury-induced alterations in miR-21 and miR-199a-3p expression can change axon growth capacity by altering overall and intra-axonal protein synthesis. Overexpression of miR-21 or inhibition of miR-199a-3p allows neurons to extend axons on the non-permissive substrate chondroitin sulfate proteoglycan (CSPG), indicating a direct impact on the neuron’s ability to extend axons over previously inhospitable terrain.

Practical Implications

Therapeutic Potential

Modulating miR-21 and miR-199a-3p levels could be a therapeutic strategy for enhancing axon regeneration after nervous system injuries.

Targeted Drug Development

Drugs targeting the PTEN/mTOR pathway via miR-21 and miR-199a-3p could promote nerve repair.

Exercise Benefits

Understanding how exercise alters miR-21 and miR-199a-3p expression can provide insights into exercise-induced neuroplasticity and recovery from SCI.

Study Limitations

1
The study primarily uses in vitro models, which may not fully replicate in vivo conditions.
2
The study focuses on specific miRs and their targets, while other factors may also contribute to axon regeneration.
3
The study uses rat models, and the findings may not be directly translatable to humans.

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