Aerobic Production and Utilization of Lactate Satisfy Increased Energy Demands Upon Neuronal Activation in Hippocampal Slices and Provide Neuroprotection Against Oxidative Stress

Lactate is moved between cells and used in the mitochondria of heart and brain cells to produce energy.

In rat brain tissue slices, lactate is used as the main fuel source for neurons during activation when glucose is unavailable, because it is converted to pyruvate by mitochondrial enzymes to sustain ATP production through the tricarboxylic acid cycle.

In rat brain tissue slices, the metabolic conversion of lactate to pyruvate produces NADH, which decreases oxidative damage caused by excessive glutamate activity and reduces exposure of neurons to reactive oxygen species.

When the enzyme that converts lactate to pyruvate is blocked in rat brain tissue slices, neurons stop functioning properly even when lactate or glucose is available as fuel, showing that lactate must be turned into pyruvate to be used for energy.

In rat brain tissue exposed to excessive glutamate, pyruvate fails to keep neurons functioning, but lactate and glucose succeed, showing pyruvate cannot replace lactate in protecting neurons under this stress.

In rat brain tissue slices, when neurons become active, they convert glucose into lactate and then use that lactate for energy, rather than relying solely on pyruvate as previously believed.