Cerebral mitochondrial metabolism in early Parkinson's disease.
Abnormal cerebral energy metabolism owing to dysfunction of mitochondrial electron transport has been implicated in the pathogenesis of Parkinson's disease (PD). However, in vivo data of mitochondrial dysfunction have been inconsistent. We directly investigated mitochondrial oxidative metabolism in vivo in 12 patients with early, never-medicated PD and 12 age-matched normal controls by combined measurements of the cerebral metabolic rate of oxygen (CMRO(2)) and the cerebral metabolic rate of glucose (CMRglc) with positron emission tomography. The primary analysis showed a statistically significant 24% increase in bihemispheric CMRO(2) and no change in CMRO(2)/CMRglc. These findings are inconsistent with a defect in mitochondrial oxidative phosphorylation owing to reduced activity of the mitochondrial electron transport system (ETS). Because PD symptoms were already manifest, deficient energy production owing to a reduced activity of the mitochondrial ETS cannot be a primary mechanism of neuronal death in early PD. Alternatively, this general increase in CMRO(2) could be due not to an increased metabolic demand but to an uncoupling of ATP production from oxidation in the terminal stage of oxidative phosphorylation. Whether this is the case in early PD and whether it is important in the pathogenesis of PD will require further study.
Powers
William J
WJ
Department of Neurology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599-7025, USA. powersw@neurology.unc.edu
Videen
Tom O
TO
Markham
Joanne
J
Black
Kevin J
KJ
Golchin
Nima
N
Perlmutter
Joel S
JS
D000328:Adult; D000368:Aged; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000378:metabolism*; D004579:Electron Transport; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography
D005947:Glucose; D010100:Oxygen