Gene expression of nAChR, SNAP-25 and GAP-43 in skeletal muscles following botulinum toxin A injection: A study in rats

Jianjun Ma, Jian Shen, Cassandra A Lee, Gamal A. Elsaidi, Thomas L. Smith, Francis O. Walker, Julia T. Rushing, Kim H. Tan, L. Andrew Koman, Beth P. Smith

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Purpose: Botulinum toxin A (BoNT-A) is used to manage spasticity in cerebral palsy. BoNT-A cleaves SNAP-25 protein, blocking acetylcholine release and weakening the muscle. Nicotinic acetylcholine receptors (nAChR) including alpha, beta, delta, gamma, and epsilon subunits, and GAP-43 protein are associated with functional recovery of neuromuscular junctions (NMJ) following BoNT-A. To better understand the mechanism behind this functional recovery, this study attempted to (1) document changes in NMJ morphometry following BoNT-A, and (2) determine the gene expression of nAChR subunits, SNAP-25, and GAP-43 protein. Methods: In this rat study (46 rats), 6 units/kg body weight of BoNT-A was injected into the gastrocnimus. NMJ morphometry and the time course of gene expression of nAChR subunits, SNAP-25, and GAP-43 were evaluated up to 1year post-injection. Results: NMJ morphometry: gutter depth was reduced vs. the control side at two months, and normalizing by 6 months following BoNT. nAChR alpha mRNA and gamma mRNA increased by 3 days, peaked at 7 days and returned to control levels; delta mRNA peaked at 3days. Epsilon mRNA peaked by 7 days. SNAP-25 mRNA increased from 60 to 90 days, returning to control levels by 6 months. GAP-43 mRNA was unchanged. Conclusions: Specific nAChR subunit mRNA expression up-regulates and then returns to normal within two weeks, preceding changes in NMJ morphometry. Although GAP-43 participates in nerve sprouting, no increase of GAP-43 mRNA occurred following BoNT-A. Delayed up-regulation of SNAP-25 mRNA might be associated with muscle functional recovery.

Original languageEnglish (US)
Pages (from-to)302-309
Number of pages8
JournalJournal of Orthopaedic Research
Volume23
Issue number2
DOIs
StatePublished - Mar 2005
Externally publishedYes

Keywords

  • Botulinum toxin
  • GAP-43
  • mRNA
  • nAChR
  • SNAP-25

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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    Ma, J., Shen, J., Lee, C. A., Elsaidi, G. A., Smith, T. L., Walker, F. O., Rushing, J. T., Tan, K. H., Koman, L. A., & Smith, B. P. (2005). Gene expression of nAChR, SNAP-25 and GAP-43 in skeletal muscles following botulinum toxin A injection: A study in rats. Journal of Orthopaedic Research, 23(2), 302-309. https://doi.org/10.1016/j.orthres.2004.08.027