Abstract
ABSTRACT
Aim
Repeated heat exposure may promote adaptive remodeling or cumulative tissue burden depending on thermal dose, but its graded molecular and functional consequences during recovery remain unclear. We examined whether repeated moderate (39°C) and severe (41°C) whole‐body hyperthermia produce distinct skeletal muscle trajectories involving mitochondrial dynamics, proteostasis, contractile gene programming, and motor behavior.
Methods
Adult male Swiss mice underwent 15‐min daily whole‐body heat exposure for 7 days at 39°C or 41°C core temperature and were assessed immediately or after 7 days of recovery. Motor and behavioral outcomes were evaluated using open‐field, elevated plus maze, grip strength, and rotarod tests. Gastrocnemius muscle was analyzed by qRT‐PCR, immunoblotting, and immunofluorescence for mitochondrial biogenesis, dynamics, mitophagy, proteostasis, and contractile phenotype markers. Cerebellar HSP60/HSP70 immunoreactivity and serum corticosterone were also assessed.
Results
At 39°C, recovery induced coordinated mitochondrial biogenesis and balanced fission‐fusion transcript upregulation. At 41°C, acute
Ppargc1a
induction (
p
p
p
p
p
p
= 5.7 × 10
−7
).
Conclusion
Moderate hyperthermia supports adaptive mitochondrial remodeling, whereas severe hyperthermia promotes stress‐related quality control, proteostatic strain, contractile suppression, and reduced grip‐related neuromuscular performance.