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

✍ Scribed by 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

• Publisher: Elsevier Science
• Year: 2005
• Tongue: English
• Weight: 762 KB
• Volume: 23
• Category: Article
• ISSN: 0736-0266
• DOI: 10.1016/j.orthres.2004.08.027

✦ Synopsis

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 1 year 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 3 days. 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. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.