Full Text:   <2716>

CLC number: R746.9

On-line Access: 2013-11-04

Received: 2013-01-21

Revision Accepted: 2013-06-03

Crosschecked: 2013-10-25

Cited: 0

Clicked: 5343

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2013 Vol.14 No.11 P.983-992


Influence of injection of Chinese botulinum toxin type A on the histomorphology and myosin heavy chain composition of rat gastrocnemius muscles

Author(s):  Bin Hong, Min Chen, Xing-yue Hu

Affiliation(s):  Department of Neurology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China; more

Corresponding email(s):   evaend@163.com, huxingyue2003@126.com

Key Words:  Botulinum toxin type A (BoNT/A), Myosin heavy chain, Chemodenervation, Remote effect

Bin Hong, Min Chen, Xing-yue Hu. Influence of injection of Chinese botulinum toxin type A on the histomorphology and myosin heavy chain composition of rat gastrocnemius muscles[J]. Journal of Zhejiang University Science B, 2013, 14(11): 983-992.

@article{title="Influence of injection of Chinese botulinum toxin type A on the histomorphology and myosin heavy chain composition of rat gastrocnemius muscles",
author="Bin Hong, Min Chen, Xing-yue Hu",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Influence of injection of Chinese botulinum toxin type A on the histomorphology and myosin heavy chain composition of rat gastrocnemius muscles
%A Bin Hong
%A Min Chen
%A Xing-yue Hu
%J Journal of Zhejiang University SCIENCE B
%V 14
%N 11
%P 983-992
%@ 1673-1581
%D 2013
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1300021

T1 - Influence of injection of Chinese botulinum toxin type A on the histomorphology and myosin heavy chain composition of rat gastrocnemius muscles
A1 - Bin Hong
A1 - Min Chen
A1 - Xing-yue Hu
J0 - Journal of Zhejiang University Science B
VL - 14
IS - 11
SP - 983
EP - 992
%@ 1673-1581
Y1 - 2013
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1300021

Background and objective: botulinum toxin type A (BoNT/A) is a metalloprotease that blocks synaptic transmission via the cleavage of a synaptosomal-associated protein of 25 kDa (SNAP-25). It has gained widespread use as a treatment for cerebral palsy and skeletal muscle hypertrophy. In China, Chinese botulinum toxin type A (CBTX-A), a type of BoNT/A, is in widespread clinical use. However, the changes in the morphological and biochemical properties of treated muscles and in remote muscles from the CBTX-A injection site are relatively unknown. Therefore, we investigated the changes in histomorphology and myosin heavy chain (MyHC) isoform composition and distribution in rat gastrocnemius muscles after intramuscular injection of CBTX-A. Methods: The weakness of the injected muscles was assessed periodically to identify their functional deficiency. Muscle slices were stained with hematoxylin-eosin (HE) and adenosine triphosphatase (ATPase). MyHC isoform composition was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to uncover changes in morphological and biochemical properties. Results: Our findings demonstrate that following injection of CBTX-A 5 U into rat gastrocnemius muscles, shifts in MyHC isoform composition emerged on the third day after injection and peaked in the fourth week. The composition remained distinctly different from that of the control group after the twelfth week. More specifically, there was a decrease in the proportion of the type IIb isoform and an increase in the proportions of type IIx, type IIa, and type I isoforms. Conclusions: Data revealed that CBTX-A led to a shift in MyHC composition towards slower isoforms and that the MyHC composition remained far from normal six months after a single injection. However, no noticeable remote muscle weakness was induced.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Ahn, J., Horn, C., Blitzer, A., 2004. Botulinum toxin for masseter reduction in Asian patients. Arch. Facial Plast. Surg., 6(3):188-191.

[2]Allen, D.L., 2008. Making sense (and antisense) of myosin heavy chain gene expression. Comments on “Intergenic bidirectional promoter and cooperative regulation of the IIx and IIb MHC genes in fast skeletal muscle” by Rinaldi et al. Am. J. Physiol. Regul. Integr. Comp. Physiol., 295(1):R206-R207.

[3]Aoki, K.R., 2001. A comparison of the safety margins of botulinum neurotoxin serotypes A, B, and F in mice. Toxicon, 39(12):1815-1820.

[4]Bentivoglio, A.R., Fasano, A., Ialongo, T., Soleti, F., Lo, F.S., Albanese, A., 2009. Fifteen-year experience in treating blepharospasm with Botox or Dysport: same toxin, two drugs. Neurotox. Res., 15(3):224-231.

[5]Biering-Sørensen, B., Kristensen, I.B., Kjaer, M., Biering-Sørensen, F., 2009. Muscle after spinal cord injury. Muscle Nerve, 40(4):499-519.

[6]DelGaudio, J.M., Sciote, J.J., 1997. Changes in myosin expression in denervated laryngeal muscle. Ann. Otol. Rhinol. Laryngol., 106(12):1076-1081.

[7]Dodd, S.L., Rowell, B.A., Vrabas, I.S., Arrowsmith, R.J., Weatherill, P.J., 1998. A comparison of the spread of three formulations of botulinum neurotoxin A as determined by effects on muscle function. Eur. J. Neurol., 5(2):181-186.

[8]Dodd, S.L., Selsby, J., Payne, A., Judge, A., Dott, C., 2005. Botulinum neurotoxin type A causes shifts in myosin heavy chain composition in muscle. Toxicon, 46(2):196-203.

[9]Drachman, D.B., Johnston, D.M., 1975. Neurotrophic regulation of dynamic properties of skeletal muscle: effects of botulinum toxin and denervation. J. Physiol., 252(3):657-667.

[10]Dressler, D., Hallett, M., 2006. Immunological aspects of Botox, Dysport and Myobloc/NeuroBloc. Eur. J. Neurol., 13(s1):11-15.

[11]Fortuna, R., Vaz, M.A., Youssef, A.R., Longino, D., Herzog, W., 2011. Changes in contractile properties of muscles receiving repeat injections of botulinum toxin (Botox). J. Biomech., 44(1):39-44.

[12]Fu, W.M., Liu, J.J., 1997. Regulation of acetylcholine release by presynaptic nicotinic receptors at developing neuromuscular synapses. Mol. Pharmacol., 51(3):390-398.

[13]Girlanda, P., Vita, G., Nicolosi, C., Milone, S., Messina, C., 1992. Botulinum toxin therapy: distant effects on neuromuscular transmission and autonomic nervous system. J. Neurol. Neurosurg. Psychiatry, 55(9):844-845.

[14]Inagi, K., Connor, N.P., Schultz, E., Ford, C.N., Cook, C.H., Heisey, D.M., 1999. Muscle fiber-type changes induced by botulinum toxin injection in the rat larynx. Otolaryngol. Head Neck Surg., 120(6):876-883.

[15]Jakubiec-Puka, A., Ciechomska, I., Morga, J., Matusiak, A., 1999. Contents of myosin heavy chains in denervated slow and fast rat leg muscles. Comp. Biochem. Physiol. B Biochem. Mol. Biol., 122(3):355-362.

[16]Kranjc, B.S., Sketelj, J., D′Albis, A., Erzen, I., 2001. Long-term changes in myosin heavy chain composition after botulinum toxin a injection into rat medial rectus muscle. Invest. Ophthalmol. Vis. Sci., 42(13):3158-3164.

[17]Lange, D.J., Rubin, M., Greene, P.E., Kang, U.J., Moskowitz, C.B., Brin, M.F., Lovelace, R.E., Fahn, S., 1991. Distant effects of locally injected botulinum toxin: a double-blind study of single fiber EMG changes. Muscle Nerve, 14(7):672-675.

[18]Larsson, L., Ansved, T., 1995. Effects of ageing on the motor unit. Prog. Neurobiol., 45(5):397-458.

[19]Lee, H.J., Lee, D.W., Park, Y.H., Cha, M.K., Kim, H.S., Ha, S.J., 2004. Botulinum toxin A for aesthetic contouring of enlarged medial gastrocnemius muscle. Dermatol. Surg., 30(6):867-871.

[20]Legerlotz, K., Matthews, K.G., McMahon, C.D., Smith, H.K., 2009. Botulinum toxin-induced paralysis leads to slower myosin heavy chain isoform composition and reduced titin content in juvenile rat gastrocnemius muscle. Muscle Nerve, 39(4):472-479.

[21]Ma, J., Elsaidi, G.A., Smith, T.L., Walker, F.O., Tan, K.H., Martin, E., Koman, L.A., Smith, B.P., 2004. Time course of recovery of juvenile skeletal muscle after botulinum toxin A injection: an animal model study. Am. J. Phys. Med. Rehabil., 83(10):774-780.

[22]Malisoux, L., Jamart, C., Delplace, K., Nielens, H., Francaux, M., Theisen, D., 2007. Effect of long-term muscle paralysis on human single fiber mechanics. J. Appl. Physiol., 102(1):340-349.

[23]Olney, R.K., Aminoff, M.J., Gelb, D.J., Lowenstein, D.H., 1988. Neuromuscular effects distant from the site of botulinum neurotoxin injection. Neurology, 38(11):1780-1783.

[24]Pette, D., Staron, R.S., 2000. Myosin isoforms, muscle fiber types, and transitions. Microsc. Res. Tech., 50(6):500-509.

[25]Rinaldi, C., Haddad, F., Bodell, P.W., Qin, A.X., Jiang, W., Baldwin, K.M., 2008. Intergenic bidirectional promoter and cooperative regulation of the IIx and IIb MHC genes in fast skeletal muscle. Am. J. Physiol. Regul. Integr. Comp. Physiol., 295(1):R208-R218.

[26]Roy, R.R., Zhong, H., Monti, R.J., Vallance, K.A., Edgerton, V.R., 2002. Mechanical properties of the electrically silent adult rat soleus muscle. Muscle Nerve, 26(3):404-412.

[27]Schiavo, G., Matteoli, M., Montecucco, C., 2000. Neurotoxins affecting neuroexocytosis. Physiol. Rev., 80(2):717-766.

[28]Talmadge, R.J., Roy, R.R., 1993. Electrophoretic separation of rat skeletal muscle myosin heavy-chain isoforms. J. Appl. Physiol., 75(5):2337-2340.

[29]Tang, X., Wan, X., 2000. Comparison of Botox with a Chinese type A botulinum toxin. Chin. Med. J. (Engl.), 113(9):794-798.

[30]Turton, K., Chaddock, J.A., Acharya, K.R., 2002. Botulinum and tetanus neurotoxins: structure, function and therapeutic utility. Trends Biochem. Sci., 27(11):552-558.

[31]Yaraskavitch, M., Leonard, T., Herzog, W., 2008. Botox produces functional weakness in non-injected muscles adjacent to the target muscle. J. Biomech., 41(4):897-902.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE