Development of a mouse model to investigate the effect of exertional heat stress on skeletal muscle

Abstract

Increased body temperature during exercise is considered a risk factor for skeletal muscle injury. There are various murine models of heat exposure-induced organ injury. The present study has attempted to develop a mouse model of skeletal muscle injury associated with exercise-induced whole body hyperthermia. C57BL/6J male mice were randomly assigned into control (CON) and exercise (EX) groups (n = 6 per group). EX group exercised on a programmed, motorized wheel, while CON group remained in a mouse cage in an environmental chamber at 35 degree C for ~3 hours. EX group showed a significantly higher average body core temperature (38.5 degree C +/- 0.3) compared to CON group (37.3 degree C +/- 0.3). Plasma myoglobin levels were significantly higher in EX group than in CON. Additionally, exercise significantly impaired skeletal muscle and mitochondria, as evidenced by elevated TBARS and caspase-3 levels and reduced ATP and Complex IV levels in gastrocnemius muscles in EX group. We developed a mouse model of exercise-induced mild whole body hyperthermia that recapitulates many key features of heat stress-induced skeletal muscle injury. This novel model will provide a useful tool for future investigation into the mechanisms of and intervention strategies for muscle exertional heat injury.