Spinal Irisin Gene Delivery Attenuates Burn Injury-Induced Muscle Atrophy by Promoting Axonal Myelination and Innervation of Neuromuscular Junctions

Int. J. Mol. Sci., 2022 · DOI: 10.3390/ijms232415899 · Published: December 14, 2022

Simple Explanation

This study investigates how delivering the irisin gene to the spinal cord can help reduce muscle loss after burn injuries. Irisin, a hormone produced during exercise, has shown promise in protecting against nerve damage in the spinal cord. The research explores whether irisin gene delivery can promote nerve regeneration and prevent muscle atrophy. The study found that delivering the irisin gene to the spinal cord helped to rehabilitate nerve fibers, improve muscle innervation, and prevent muscle weakness and loss after burn injuries. This suggests that irisin plays a key role in maintaining the connection between nerves and muscles, which is crucial for muscle health. Researchers examined the impact of irisin on specific proteins and factors involved in muscle growth and nerve function. They discovered that irisin can modulate the levels of certain neurotrophic factors, such as BDNF and GDNF, which are essential for nerve regeneration and muscle health, suggesting a complex interplay between irisin and these factors.

Study Duration

Not specified

Participants

Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
Spinal irisin gene delivery attenuates burn injury-induced sciatic nerve demyelination and reduction of neuromuscular junction innervation.
2
Spinal overexpression of irisin leads to myelination rehabilitation and muscular innervation through the modulation of brain-derived neurotrophic factor and glial-cell-line-derived neurotrophic factor expression along the sciatic nerve to the muscle tissues.
3
Spinal irisin gene delivery modulates BDNF and GDNF expression in the ventral horn and sciatic nerve after burn injury.

Research Summary

The study validates that burn injury results in sciatic nerve demyelination and that Schwann cell dedifferentiation increases the expression of the immature marker p75 and reduces that of the maturated marker MBP. Spinal irisin gene delivery attenuates burn injury, which results from neuromuscular junction dysregulation caused by the interplay between the co-maturation of muscle and motor neuron progenitor cells in the muscle regenerative process after burn injury. Spinal irisin gene delivery normalized balance between pro-BDNF and mBDNF might be involved in rehabilitation of neuromuscular junctions after burn injury.

Practical Implications

Therapeutic Potential

Spinal irisin gene delivery shows promise as a therapeutic intervention to combat muscle atrophy and neuropathy following burn injuries.

Underlying Mechanisms

The study enhances understanding of the molecular mechanisms through which irisin promotes nerve regeneration, myelination, and muscle health, opening avenues for targeted therapies.

Clinical Translation

The findings support the exploration of irisin-based therapies to improve rehabilitation outcomes and quality of life for burn survivors.

Study Limitations

1
The study focuses on a rodent model, and further research is needed to validate the findings in human subjects.
2
The long-term effects of spinal irisin gene delivery and its potential side effects require further investigation.
3
The specific mechanisms through which irisin interacts with BDNF and GDNF to promote nerve regeneration warrant further elucidation.

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