Jaime M. Ross1,2, Johana berg3,
Stefan Bren4, Giuseppe Coppotelli5, Mgen Terzioglu6,
Karin Pernold1, Rouslan Sitnikov3, Jan Kehr7,
Alexandra Trifunovic6, Nils-Gran Larsson6,8, Barry J.
Hoffer2, Lars Olson1
1Neuroscience, Karolinska Institutet,
Stockholm, Sweden; 2National Institute on Drug Abuse, National
Institutes of Health, Baltimore, MD, United States; 3Clinical
Science, Intervention and Technology, Karolinska Institutet, Stockholm,
Sweden; 4Neurobiology, Health Sciences and Society, Karolinska
Institutet, Stockholm, Sweden; 5Cell and Molecular Biology,
Karolinska Institutet, Stockholm, Sweden; 6Laboratory Medicine,
Karolinska Institutet, Stockholm, Sweden; 7Physiology and
Pharmacology, Karolinska Institutet, Stockholm, Sweden; 8Max
Planck Institute for Biology of Ageing, Cologne, Germany
The
prematurely ageing mtDNA mutator mouse was used to study mitochondrial
dysfunction in the brain. 1H-MRS detected a 2-fold increase in
cortical and striatal lactate levels as early as 6-9 weeks and continued
throughout the lives of mtDNA mutator mice (average life span 45-48 weeks).
Increased brain lactate levels were confirmed postmortem by high-performance
liquid chromatography (HPLC). These methods revealed that abnormally high
lactate levels in the CNS are an early phenotype of premature ageing in the
mtDNA mutator mouse. Our data support the hypothesis of abnormal metabolism
in ageing due to mitochondrial dysfunction.