Agrin Inﬂuences Botulinum Neurotoxin A-Induced Nerve Sprouting via miR-144-agrin-MuSK Signaling

Frontiers in Cell and Developmental Biology, 2020 · DOI: 10.3389/fcell.2020.00015 · Published: January 30, 2020

Simple Explanation

Botulinum neurotoxin (BoNT) is used to treat neurological disorders and for aesthetic purposes, but its effects are limited by nerve sprouting. This study explores the role of agrin in BoNT/A-induced nerve sprouting. The researchers found that agrin is involved in regulating nerve sprouting caused by BoNT/A. Blocking agrin with an anti-agrin antibody can prolong the effect of BoNT/A. Agrin influences the duration of BoNT/A's effect by regulating MuSK and is itself regulated by miR-144. Thus, agrin could be a target for prolonging BoNT/A's effects.

Study Duration

12 weeks

Participants

Male Sprague-Dawley rats (200–220 g) and rats at the 1st, 4th, and 8th week after birth

Evidence Level

Not specified

Key Findings

1
Agrin participates in regulating nerve sprouting after BoNT/A application, indicated by increased agrin expression at NMJs after BoNT/A injection.
2
Agrin-Ab prevents the recovery of muscle strength and prolongs the duration of BoNT/A effect in a dose-dependent manner, suggesting agrin can serve as an interventional target.
3
Agrin influences the duration of BoNT/A effect by regulating downstream MuSK, showing that agrin-Ab delays the increase of MuSK expression.

Research Summary

This study investigates the role of agrin in BoNT/A-induced nerve sprouting in rats. The aim was to determine if agrin could serve as a target for prolonging BoNT/A's effect and to understand the regulatory mechanisms involved. The results showed that agrin is involved in regulating BoNT/A-induced nerve sprouting. Blocking agrin function with anti-agrin antibody delayed muscle strength recovery and prolonged the duration of BoNT/A's effect. Agrin influences BoNT/A's duration of effect by regulating downstream MuSK and is simultaneously regulated by upstream miR-144, suggesting agrin could find clinical application as an interventional target.

Practical Implications

Therapeutic Target

Agrin could be a potential therapeutic target for prolonging the effects of BoNT/A, reducing the frequency of injections.

Interventional Strategy

Using anti-agrin antibodies or other methods to block agrin function could delay muscle strength recovery and extend the duration of BoNT/A's effects.

Signaling Pathway

Understanding the miR-144-agrin-MuSK signaling pathway could lead to the development of new interventions for nerve sprouting and neuromuscular junction maintenance.

Study Limitations

1
The effect of exogenous IgG protein was not excluded.
2
In vivo and in vitro studies are required to elucidate the regulatory role of miR-144/agrin/MuSK signaling in the development of NMJs.
3
Not specified

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