The effect of L-lactate on long term memory through NMDA receptor

In the brain glycogen the storage form of glucose is exclusively localized in astrocytes. Glycogenolysis leads to the production of L-lactate which is shuttled to neurons for ATP production. Interestingly L-lactate was recently shown to be not only a source of energy but also a signaling molecule to neurons. This was demonstrated through the inhibition of L-lactate production or transport in an inhibitory avoidance paradigm where the rodents developed amnesia. This inhibition of memory consolidation was rescued by L-lactate and not by equicaloric glucose emphasizing that L-lactate acts as a signaling molecule as well. A recent study in our laboratory suggests that the action of L-lactate takes place through a cascade of molecular events via the modulation of N-methyl-D-aspartate receptor (NMDAR) activity. Since NADH produced similar results to those seen with L-lactate it was hypothesized that the action of the latter is based on altering the redox state of the cell in particular in view of the fact that redox-sensitive sites are present on the NMDAR. However the precise molecular mechanism underlying the apparent change in the NMDAR activity is not fully elucidated.