Lactate brain metabolism in different mouse strains probed by hyperpolarized 13C MRS

Lactate plays an important role in brain energetics and is essential for neuronal function. Alteration of its metabolism might be associated with mechanisms linked to neurodegenerative disorders1. The purpose of this study was to demonstrate the potential of of hyperpolarized [1-13C] lactate to sudy brain metabolism in mice. Following injection, hyperpolarized [1-13C] lactate is transferred through the blood brain barrier (BBB) via monocarboxylate transporters (MCTs), in particular MCT12. These transporters are thought to play an important role in neurodegenerative diseases but their concentration in different mice strains is not understood well. We performed real-time 13C metabolic studies with hyperpolarized [1-13C] lactate in two different mouse strains, namely NMRI mouse and C57BL/6. We could readily detect the signals of [1-13C] pyruvate, [1-13C] alanine and 13C bicarbonate. We observed a significant difference in the dynamics of lactate to pyruvate conversion between the two mouse strains. This demonstrates that the kinetics of lactate transport across the BBB is not identical in all mice strains and care should be taken when comparing metabolic processes between different animal types and in particular genetically modified strains used to study neurodegenerative disorders.