Bioenergetic Evaluation of Muscle Fatigue in Murine Tongue

Abstract

Muscle fatigue is the diminution of force required for a particular action over time. Fatigue may be particularly pronounced in aging muscles, including those used for swallowing actions. Because risk for swallowing impairment (dysphagia) increases with aging, the contribution of muscle fatigue to age-related dysphagia is an emerging area of interest. The use of animal models, such as mice and rats (murine models) allows experimental paradigms for studying the relationship between muscle fatigue and swallowing function with a high degree of biological precision that is not possible in human studies. The goal of this article is to review basic experimental approaches to the study of murine tongue muscle fatigue related to dysphagia. Traditionally, murine muscle fatigue has been studied in limb muscles through direct muscle stimulation and behavioral exercise paradigms. As such, physiological and bioenergetic markers of muscle fatigue that have been validated in limb muscles may be applicable in studies of cranial muscle fatigue with appropriate modifications to account for differences in muscle architecture, innervation ratio, and skeletal support. Murine exercise paradigms may be used to elicit acute fatigue in tongue muscles, thereby enabling study of putative muscular adaptations. Using these approaches, hypotheses can be developed and tested in mice and rats to allow for future focused studies in human subjects geared toward developing and optimizing treatments for age-related dysphagia.

Keywords: Ageing; Dysphagia; Exercise; Fatigue; Murine; Tongue.

Fig. 1

Treadmill exercise may engage both limb muscles and tongue muscles. Descriptive caption: An outline illustration depicting a rat running, with labels indicating tongue muscles (airway geometry) and limb muscles (running)

Fig. 2

Acute fatigue was shown in both soleus (sol) and styloglossus (SG) muscles through reductions of muscle glycogen in a treadmill exercise condition as compared to control groups (*; p < .05), (**; p ≤ .01). Tissues were isolated for analysis immediately following exercise. Con Control condition, GG genioglossus muscle

Fig. 3

Following treadmill running to a state of fatigue, gene expression of Slc25a25 in soleus and SG muscles was significantly greater in the fatigue group (**; p ≤ .01) than the sedentary control group. Soleus additionally showed higher expression levels of citrate synthase (Cs) in the fatigue group than in the control group. (*; p < .05). Tissues were isolated for analysis immediately following exercise