Cerebral oxygen and glucose metabolism in patients with mitochondrial m.3243A > G mutation

Markus M. Lindroos, Ronald J. Borra, Riitta Parkkola, Sami M. Virtanen, Virva Lepomaki, Marco Bucci, Jere R. Virta, Juha O. Rinne, Pirjo Nuutila, Kari Majamaa*

*Corresponding author voor dit werk

    OnderzoeksoutputAcademicpeer review

    28 Citaten (Scopus)

    Samenvatting

    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-[F-18]fluoro-2-deoxyglucose, [O-15]H2O and [O-15]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.

    Originele taal-2English
    Pagina's (van-tot)3274-3284
    Aantal pagina's11
    TijdschriftBrain
    Volume132
    Nummer van het tijdschrift12
    DOI's
    StatusPublished - dec.-2009

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