Investigation of effects of repeated hyperthermia on skeletal muscle and motor function in mice

This study explored the impact of repeated hyperthermia on mitochondrial function, proteostasis in mice, and consequent effects on motor and anxiety-like behaviors. Forty Swiss male mice were divided into five groups: Control Exposure (con-E), 39°C/15 minutes/7 days (39E), 41°C/15 minutes/7 days (41E), Control Exposure and Recovery (con-ER), 39°C/15 minutes/7 days with 7-days recovery (39ER), and 41°C/15 minutes/7 days with 7-days recovery (41ER). Post-exposure, the 41E group showed muscle weakness (p<0.05), and both 39E and 41E exhibited anxiety-like behavior on the EPM test (p<0.05). Gene analysis from gastrocnemius tissues demonstrated altered mRNA expression. Both 39E and 41E had reduced Pgc-1α levels (p<0.05). Pgc-1β expression notably differed, between 39E and 41ER (p<0.01), 39ER and 41ER (p<0.01), and 41ER (p<0.01). There was a significant difference in TFAM expression between 39E and 41ER (p<0.01). The 39ER group had increased NRF1 (p<0.05). PINK1, affected by temperature, differed between 39E and 41E (p<0.05). PARKIN showcased recovery effects between 41E and 41ER (p<0.01). Ucp2 levels contrasted between 39ER and 41ER (p<0.05). In summary, mild temperatures (39°C) suppressed autophagy, maintaining strength, and initiating the Nrf1-Tfam-Ucp2 pathway post-recovery whereas muscle strength decreased. Severe temperatures (41°C) caused mitochondrial dysfunction and muscle strength decline. Recovery induced increase in Pgc-1β modulated mitochondrial biogenesis and in Parkin indicates mitophagy. Moderate hyperthermia induced apparent anxiety-like behaviors in the acute phase, which subsided after the recovery period. Key words: Repeated Hyperthermia, Mitochondria, Skeletal Muscle, Motor Function