Diminished lactate utilization in LDHB-deficient neurons leads to impaired long-term memory retention

The brain's substantial energy consumption primarily arises from the continuous activity of its neurons, which are involved in information processing, transmission, and storage. The astrocyte-neuron lactate shuttle (ANLS) suggests that neurons preferentially utilize lactate over glucose due to its higher efficiency. Astrocytes are proposed to supply neurons with lactate through LDHA expression, while neurons predominantly express LDHB to facilitate lactate oxidation. In this study, LDHB-deficient neurons demonstrated reduced capacity to utilize lactate, which correlated with impaired long-term memory retention in LDHB-deficient mice. However, these mice retained normal short-term memory and showed no macroscopic brain anomalies or neuronal cell death. In a high-glucose environment, the energy metabolism of LDHB-deficient neurons remained typical, suggesting that lactate is not the sole or primary substrate for neuronal energy metabolism, with glucose and other substrates sufficiently supporting the requirements. The observed expression of LDHA in neurons further corroborates the glucose-driven energy metabolism in these cells