Cerebral oxygen and glucose metabolism in patients with mitochondrial m.3243A>G mutation.
The m.3243A>G mutation is the most common pathogenic mutation in mitochondrial DNA. It leads to defective oxidative phosphorylation, decreased oxygen consumption and increased glucose utilization and lactate production in vitro. However, oxygen and glucose metabolism has not been studied in the brain of patients harbouring the m.3243A>G mutation. Therefore, 14 patients with the m.3243A>G mutation, not experiencing acute stroke-like episodes and 14 age-matched controls underwent positron emission tomography using 2-[(18)F]fluoro-2-deoxyglucose, [(15)O]H(2)O and [(15)O]O(2) as the tracers during normoglycaemia. The metabolic rate of oxygen and glucose were determined using a quantitative region of interest analysis. Metabolites in unaffected periventricular tissue were measured using magnetic resonance spectroscopy. We found that the cerebral metabolic rate of oxygen was decreased by 26% (range 18%-29%) in the grey as well as the white matter of patients with the m.3243A>G mutation. A decrease in the metabolic rate of glucose was found with predilection to the posterior part of the brain. No major changes were detected in cerebral blood flow or the number of white matter lesions. Our results show that the m.3243A>G mutation leads to a global decrease in oxygen consumption in the grey matter including areas where no other signs of disease were present.
Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.
Markus M
MM
Lindroos
Ronald J
RJ
Borra
Riitta
R
Parkkola
Sami M
SM
Virtanen
Virva
V
Lepomäki
Marco
M
Bucci
Jere R
JR
Virta
Juha O
JO
Rinne
Pirjo
P
Nuutila
Kari
K
Majamaa
D000328:Adult; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D001928:Brain Diseases, Metabolic / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005947:Glucose / Q000378:metabolism; D006801:Humans; D002534:Hypoxia, Brain / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010101:Oxygen Consumption / Q000235:genetics; D049268:Positron-Emission Tomography
D024101:Mitochondrial Proteins; D005947:Glucose