Impaired exercise capacity, but unaltered mitochondrial respiration in skeletal or cardiac muscle of mice lacking cellular prion protein

The studies of physiological roles for cellular prion protein (PrPc) have focused on possible functions of this protein in the CNS, where it is largely expressed. However, the observation that PrPc is expressed also in muscle tissue suggests that the physiological role of PrPc might not be limited to the central nervous system. In the present study, we investigated possible functions of PrPc in muscle using PrPc gene (Prnp) null mice (Prnp0/0). For this purpose, we submitted Prnp0/0 animals to different protocols of exercise, and compared their performance to that of their respective wild-type controls. Prnp0/0 mice showed an exercise-dependent impairment of locomotor activity. In searching for possible mechanisms associated with the impairment observed, we evaluated mitochondrial respiration (MR) in skeletal or cardiac muscle from these mice during resting or after different intensities of exercise. Baseline MR (states 3 and 4), respiratory control ratio (RCR) and mitochondrial membrane potential (ΔΨ) were evaluated and were not different in skeletal or cardiac muscle tissue of Prnp0/0 mice when compared with wild-type animals. We concluded that Prnp0/0 mice show impairment of swimming capacity, perhaps reflecting impairment of muscular activity under more extreme exercise conditions. In spite of the mitochondrial abnormalities reported in Prnp0/0 mice, our observation seems not to be related to MR. Our results indicate that further investigations should be conducted in order to improve our knowledge about the function of PrPc in muscle physiology and its possible role in several different neuromuscular pathologies.