Abstract #2393

Elevated Brain Lactate Measured by 1H-MRS Is an Early Phenotype Due to Mitochondrial Dysfunction in the Prematurely Ageing MtDNA Mutator Mouse

Jaime M. Ross^1,2, Johana berg³, Stefan Bren⁴, Giuseppe Coppotelli⁵, Mgen Terzioglu⁶, Karin Pernold¹, Rouslan Sitnikov³, Jan Kehr⁷, Alexandra Trifunovic⁶, Nils-Gran Larsson^6,8, 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.