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

30 Citations (Scopus)

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

Fingerprint

GAP-43 Protein
Type A Botulinum Toxins
Nicotinic Receptors
Skeletal Muscle
Gene Expression
Neuromuscular Junction
Messenger RNA
Injections
Up-Regulation
Synaptosomal-Associated Protein 25
Muscles
Cerebral Palsy
Acetylcholine
Body Weight

Keywords

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

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Gene expression of nAChR, SNAP-25 and GAP-43 in skeletal muscles following botulinum toxin A injection : A study in rats. / Ma, Jianjun; Shen, Jian; Lee, Cassandra A; Elsaidi, Gamal A.; Smith, Thomas L.; Walker, Francis O.; Rushing, Julia T.; Tan, Kim H.; Koman, L. Andrew; Smith, Beth P.

In: Journal of Orthopaedic Research, Vol. 23, No. 2, 03.2005, p. 302-309.

Research output: Contribution to journalArticle

Ma, J, Shen, J, Lee, CA, Elsaidi, GA, Smith, TL, Walker, FO, Rushing, JT, Tan, KH, Koman, LA & Smith, BP 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, vol. 23, no. 2, pp. 302-309. https://doi.org/10.1016/j.orthres.2004.08.027
Ma, Jianjun ; Shen, Jian ; Lee, Cassandra A ; Elsaidi, Gamal A. ; Smith, Thomas L. ; Walker, Francis O. ; Rushing, Julia T. ; Tan, Kim H. ; Koman, L. Andrew ; Smith, Beth P. / Gene expression of nAChR, SNAP-25 and GAP-43 in skeletal muscles following botulinum toxin A injection : A study in rats. In: Journal of Orthopaedic Research. 2005 ; Vol. 23, No. 2. pp. 302-309.
@article{85989284b33848aab149037836cf88c0,
title = "Gene expression of nAChR, SNAP-25 and GAP-43 in skeletal muscles following botulinum toxin A injection: A study in rats",
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.",
keywords = "Botulinum toxin, GAP-43, mRNA, nAChR, SNAP-25",
author = "Jianjun Ma and Jian Shen and Lee, {Cassandra A} and Elsaidi, {Gamal A.} and Smith, {Thomas L.} and Walker, {Francis O.} and Rushing, {Julia T.} and Tan, {Kim H.} and Koman, {L. Andrew} and Smith, {Beth P.}",
year = "2005",
month = "3",
doi = "10.1016/j.orthres.2004.08.027",
language = "English (US)",
volume = "23",
pages = "302--309",
journal = "Journal of Orthopaedic Research",
issn = "0736-0266",
publisher = "John Wiley and Sons Inc.",
number = "2",

}

TY - JOUR

T1 - Gene expression of nAChR, SNAP-25 and GAP-43 in skeletal muscles following botulinum toxin A injection

T2 - A study in rats

AU - Ma, Jianjun

AU - Shen, Jian

AU - Lee, Cassandra A

AU - Elsaidi, Gamal A.

AU - Smith, Thomas L.

AU - Walker, Francis O.

AU - Rushing, Julia T.

AU - Tan, Kim H.

AU - Koman, L. Andrew

AU - Smith, Beth P.

PY - 2005/3

Y1 - 2005/3

N2 - 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.

AB - 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.

KW - Botulinum toxin

KW - GAP-43

KW - mRNA

KW - nAChR

KW - SNAP-25

UR - http://www.scopus.com/inward/record.url?scp=20044386651&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20044386651&partnerID=8YFLogxK

U2 - 10.1016/j.orthres.2004.08.027

DO - 10.1016/j.orthres.2004.08.027

M3 - Article

C2 - 15734240

AN - SCOPUS:20044386651

VL - 23

SP - 302

EP - 309

JO - Journal of Orthopaedic Research

JF - Journal of Orthopaedic Research

SN - 0736-0266

IS - 2

ER -