Skeletal muscle properties in a transgenic mouse model for amyotrophic lateral sclerosis: effects of creatine treatment.
The present study was undertaken to identify the metabolic and contractile characteristics of fast- and slow-twitch skeletal muscles in a transgenic mouse model of amyotrophic lateral sclerosis (ALS). In addition, we investigated the effects of oral creatine supplementation on muscle functional capacity in this model. Transgenic mice expressing a mutant (G93A) or wild type human SOD1 gene (WT) were supplemented with 2% creatine monohydrate from 60 to 120 days of age. Body weight, rotorod performance and grip strength were evaluated. In vitro contractility was evaluated on isolated m. soleus and m. extensor digitorum longus (EDL), and muscle metabolites were determined. Body weight, rotorod performance and grip strength were markedly decreased in G93A compared to WT mice, but were unaffected by creatine supplementation. Muscle ATP content decreased and glycogen content increased in G93A versus WT in both muscle types, but were unaffected by creatine supplementation. Muscle creatine content increased following creatine intake in G93A soleus. Twitch and tetanic contractions showed markedly slower contraction and relaxation times in G93A versus WT in both muscle types, with no positive effect of creatine supplementation. EDL but not soleus of G93A mice showed significant atrophy, which was partly abolished by creatine supplementation. It is concluded that overexpression of a mutant SOD1 transgene has profound effects on metabolic and contractile properties of both fast- and slow-twitch skeletal muscles. Furthermore, creatine intake does not exert a beneficial effect on muscle function in a transgenic mouse model of ALS.
Derave
Wim
W
Exercise Physiology and Biomechanics Laboratory, Department of Kinesiology, Faculty of Physical Education and Physiotherapy, K.U. Leuven, B-3001, Leuven, Belgium. wim.derave@flok.kuleuven.ac.be
Van Den Bosch
Ludo
L
Lemmens
Griet
G
Eijnde
Bert O
BO
Robberecht
Wim
W
Hespel
Peter
P
D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000503:physiopathology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003401:Creatine / Q000627:therapeutic use*; D006003:Glycogen / Q000032:analysis / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009119:Muscle Contraction / Q000187:drug effects / Q000235:genetics; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000378:metabolism; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D009133:Muscular Atrophy / Q000235:genetics; D009154:Mutation; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
C000606290:SOD1 protein, human; D000255:Adenosine Triphosphate; D006003:Glycogen; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D003401:Creatine