Effect of unacylated ghrelin on peripheral nerve regeneration

European Journal of Histochemistry, 2021 · DOI: 10.4081/ejh.2021.3287 · Published: August 13, 2021

Endocrinology Neurology Regenerative Medicine & Stem Cells

Simple Explanation

This study investigates the role of unacylated ghrelin (UnAG) in peripheral nerve regeneration after injury. The researchers used transgenic mice with elevated UnAG levels to examine its impact on nerve regeneration following both a crush injury and a surgically repaired nerve transection. The study found that UnAG may play a role in the development of peripheral nerves, as evidenced by differences in nerve structure between normal mice and those with elevated UnAG. Furthermore, UnAG appeared to promote faster recovery after a more severe nerve injury that required surgical repair. These findings suggest UnAG could be a potential therapeutic target for promoting nerve regeneration, especially in cases of severe nerve damage. Further research is needed to understand how UnAG works and to develop drugs that can effectively harness its regenerative properties.

Study Duration

25 days for crush injury groups, 70 days for end-to-end repair groups

Participants

30 adult female FVB mice

Evidence Level

Not specified

Key Findings

1
Healthy mice with elevated UnAG levels showed differences in nerve structure compared to normal mice, suggesting a role for UnAG in nerve development. Specifically, UnAG median nerves have a higher density and smaller myelinated fibres than WT nerves.
2
After a crush injury, UnAG did not significantly affect nerve regeneration. No significant differences were observed between WT and UnAG regenerated groups after crush injury in any of the analysed time points.
3
Following surgical repair of a nerve transection, mice with elevated UnAG showed faster functional recovery compared to normal mice. functional analysis showed a faster recovery in UnAG group since at day 35 values of grasping test are significantly higher than WT group.

Research Summary

This study evaluated the impact of unacylated ghrelin (UnAG) on peripheral nerve regeneration in mice after crush and transection injuries. The researchers used transgenic mice with overexpression of the ghrelin gene, leading to elevated UnAG levels. The analysis of healthy median nerves of both WT and UnAG nerves showed that UnAG median nerves have a higher density and smaller myelinated fibres than WT nerves. These results suggest a possible role of UnAG in development that have to be deepened. The study concluded that UnAG could have a therapeutic role in promoting regeneration after more severe lesions, as indicated by faster recovery after EtE repair. By providing the proof of principle that UnAG promotes regeneration of injured peripheral nerves, these finding may spur further research aimed to identify the still unknown receptor mediating UnAG biological effects.

Practical Implications

Potential Therapeutic Target

Unacylated ghrelin (UnAG) could be a therapeutic target for enhancing peripheral nerve regeneration, especially after severe injuries.

Understanding UnAG Mechanism

Further research is needed to identify the receptor mediating UnAG's regenerative effects to develop targeted therapies.

Drug Development

Identification of the novel UnAG receptor will allow both the characterization of the mechanisms regulating its regenerative activity and the development of synthetic UnAG receptor agonists featuring pharmacological properties more suitable for therapeutic applications than UnAG

Study Limitations

1
The study was conducted on mice and may not directly translate to humans.
2
The specific mechanisms by which UnAG promotes nerve regeneration remain unclear.
3
The UnAG receptor has not yet been identified, limiting the ability to develop targeted therapies.

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