Systems analysis of transcriptional data provides insights into muscle's biological response to botulinum toxin.

TitleSystems analysis of transcriptional data provides insights into muscle's biological response to botulinum toxin.
Publication TypeJournal Article
Year of Publication2014
AuthorsMukund K, Mathewson M, Minamoto V, Ward SR, Subramaniam S, Lieber RL
JournalMuscle Nerve
Volume50
Issue5
Pagination744-58
Date Published2014 Nov
ISSN1097-4598
KeywordsAcetylcholine Release Inhibitors, Adaptation, Physiological, Animals, Botulinum Toxins, Type A, Extracellular Matrix, Gene Expression Profiling, Male, Mitochondrial Turnover, Muscle Contraction, Muscle, Skeletal, Muscular Atrophy, Neuromuscular Junction, Oligonucleotide Array Sequence Analysis, Oxidative Stress, Rats, Rats, Sprague-Dawley, Statistics as Topic, Time Factors, Transcriptional Activation
Abstract

INTRODUCTION: This study provides global transcriptomic profiling and analysis of botulinum toxin A (BoNT-A)-treated muscle over a 1-year period.

METHODS: Microarray analysis was performed on rat tibialis anterior muscles from 4 groups (n = 4/group) at 1, 4, 12, and 52 weeks after BoNT-A injection compared with saline-injected rats at 12 weeks.

RESULTS: Dramatic transcriptional adaptation occurred at 1 week with a paradoxical increase in expression of slow and immature isoforms, activation of genes in competing pathways of repair and atrophy, impaired mitochondrial biogenesis, and increased metal ion imbalance. Adaptations of the basal lamina and fibrillar extracellular matrix (ECM) occurred by 4 weeks. The muscle transcriptome returned to its unperturbed state 12 weeks after injection.

CONCLUSIONS: Acute transcriptional adaptations resemble denervated muscle with some subtle differences, but resolved more quickly compared with denervation. Overall, gene expression across time correlates with the generally accepted BoNT-A time course and suggests that the direct action of BoNT-A in skeletal muscle is relatively rapid.

DOI10.1002/mus.24211
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/24536034?dopt=Abstract
Alternate JournalMuscle Nerve
PubMed ID24536034
PubMed Central IDPMC4136975
Grant ListAR057013 / AR / NIAMS NIH HHS / United States
HL087375-02 / HL / NHLBI NIH HHS / United States
HL106579 / HL / NHLBI NIH HHS / United States
HL108735 / HL / NHLBI NIH HHS / United States
R24 HD050837 / HD / NICHD NIH HHS / United States
R24HD050837 / HD / NICHD NIH HHS / United States
Track(s): 
Bioinformatics and Systems Biology