Non-invasive muscle contraction assay to study rodent models of sarcopenia.
BACKGROUND
Age-related sarcopenia is a disease state of loss of muscle mass and strength that affects physical function and mobility leading to falls, fractures, and disability. The need for therapies to treat age-related sarcopenia has attracted intensive preclinical research. To facilitate the discovery of these therapies, we have developed a non-invasive rat muscle functional assay system to efficiently measure muscle force and evaluate the efficacy of drug candidates.


METHODS
The lower leg muscles of anesthetized rats are artificially stimulated with surface electrodes on the knee holders and the heel support, causing the lower leg muscles to push isometric pedals that are attached to force transducers. We developed a stimulation protocol to perform a fatigability test that reveals functional muscle parameters like maximal force, the rate of fatigue, fatigue-resistant force, as well as a fatigable muscle force index. The system is evaluated in a rat aging model and a rat glucocorticoid-induced muscle loss model


RESULTS
The aged rats were generally weaker than adult rats and showed a greater reduction in their fatigable force when compared to their fatigue-resistant force. Glucocorticoid treated rats mostly lost fatigable force and fatigued at a higher rate, indicating reduced force from glycolytic fibers with reduced energy reserves.


CONCLUSIONS
The involuntary contraction assay is a reliable system to assess muscle function in rodents and can be applied in preclinical research, including age-related sarcopenia and other myopathy.
Department of Molecular Endocrinology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Chi-Sung
CS
Chiu
Hans
H
Weber
Sharon
S
Adamski
Albert
A
Rauch
Michael A
MA
Gentile
Stephen E
SE
Alves
Gary
G
Kath
Osvaldo
O
Flores
Hilary A
HA
Wilkinson
D000367:Age Factors; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001681:Biological Assay; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005938:Glucocorticoids / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018763:Muscle Fatigue / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055948:Sarcopenia / Q000503:physiopathology*
D005938:Glucocorticoids; D003907:Dexamethasone