Analysis of neuron-astrocyte metabolic cooperation in the brain of db/db mice with cognitive decline using 13C NMR spectroscopy

Type 2 diabetes has been linked to cognitive impairment, but its potential metabolic mechanism is still unclear. The present study aimed to explore neuron-astrocyte metabolic cooperation in the brain of diabetic (db/db, BKS. Cg-m(+/+) Leprdb/J) mice with cognitive decline using C-13 NMR technique in combination with intravenous [2-(CC)-C-13]-acetate and [3-(CC)-C-13]-lactate infusions. We found that the C-13-enrichment from [2-(CC)-C-13]-acetate into tricarboxylic acid cycle intermediate, succinate, was significantly decreased in db/db mice with cognitive decline compared with wild-type (WT, C57BLKS/J) mice, while an opposite result was obtained after [3-(CC)-C-13]-lactate infusion. Relative to WT mice, db/db mice with cognitive decline had significantly lower (CC)-C-13 labeling percentages in neurotransmitters including glutamine, glutamate, and g-aminobutyric acid after [2-(CC)-C-13]-acetate infusion. However, [3-(CC)-C-13]-lactate resulted in increased (CC)-C-13-enrichments in neurotransmitters in db/db mice with cognitive decline. This may indicate that the disturbance of neurotransmitter metabolism occurred during the development of cognitive decline. In addition, a reduction in (CC)-C-13-labeling of lactate and an increase in gluconeogenesis were found from both labeled infusions in db/db mice with cognitive decline. Therefore, our results suggest that the development of cognitive decline in type 2 diabetes may be implicated to an unbalanced metabolism in neuron-astrocyte cooperation and an enhancement of gluconeogenesis.