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 (PrP(c)) have focused on possible functions of this protein in the CNS, where it is largely expressed. However, the observation that PrP(c) is expressed also in muscle tissue suggests that the physiological role of PrP(c) might not be limited to the central nervous system. In the present study, we investigated possible functions of PrP(c) in muscle using PrP(c) gene (Prnp) null mice (Prnp(0/0)). For this purpose, we submitted Prnp(0/0) animals to different protocols of exercise, and compared their performance to that of their respective wild-type controls. Prnp(0/0) 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 (DeltaPsi) were evaluated and were not different in skeletal or cardiac muscle tissue of Prnp(0/0) mice when compared with wild-type animals. We concluded that Prnp(0/0) 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 Prnp(0/0) 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 PrP(c) in muscle physiology and its possible role in several different neuromuscular pathologies.
Nico
Patrícia Barreto Costa
PB
Departamento de Neurologia, Psiquiatria e Psicologia Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (FMRP-USP), Hospital das Clínicas/CIREP, Campus Universitário-Monte Alegre, Ribeirão Preto, SP 14048 900, Brazil.
Lobão-Soares
Bruno
B
Landemberger
Michele Christine
MC
Marques
Wilson
W
Tasca
Carla I
CI
de Mello
Carlos Fernando
CF
Walz
Roger
R
Carlotti
Carlos Gilberto
CG
Brentani
Ricardo R
RR
Sakamoto
Américo C
AC
Bianchin
Marino Muxfeldt
MM
D000818:Animals; D019069:Cell Respiration / Q000235:genetics / Q000502:physiology*; D017079:Exercise Tolerance / Q000235:genetics*; D005609:Free Radicals / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009043:Motor Activity / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D018621:PrPC Proteins / Q000378:metabolism*; D013550:Swimming / Q000502:physiology
D005609:Free Radicals; D018621:PrPC Proteins