title: Systems analysis of transcriptional data provides insights into muscle's biological response to botulinum toxin.
abstract: BACKGROUND
  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.
authors.affiliation: Bioinformatics and System Biology Graduate Program, University of California San Diego, La Jolla, California, USA.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Mukund
authors.forename: Margie
authors.initials: M
authors.lastname: Mathewson
authors.forename: Viviane
authors.initials: V
authors.lastname: Minamoto
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Ward
authors.forename: Shankar
authors.initials: S
authors.lastname: Subramaniam
authors.forename: Richard L
authors.initials: RL
authors.lastname: Lieber
mesh_terms: D065087:Acetylcholine Release Inhibitors / Q000494:pharmacology*; D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D008297:Male; D063269:Mitochondrial Turnover / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009133:Muscular Atrophy / Q000139:chemically induced / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013223:Statistics as Topic; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: D065087:Acetylcholine Release Inhibitors; D019274:Botulinum Toxins, Type A
keywords: botulinum toxin A; cross-sectional study; microarray gene expression; neurotoxin; skeletal muscle; time course