Glucose and lactate metabolism during brain activation

The dependence of brain function on blood glucose as a fuel does not exclud e the possibility that lactate within the brain might be transferred betwee n different cell types and serve as an energy source. It has been recently suggested that 1) about 85% of glucose consumption during brain activation is initiated by aerobic glycolysis in astrocytes, triggered by demand for g lycolytically derived energy for Na+-dependent accumulation of transmitter glutamate and its amidation to glutamine, and 2) the generated lactate is q uantitatively transferred to neurons for oxidative degradation. However, as trocytic glutamate uptake can be fuelled by either glycolytically or oxidat ively derived energy, and the extent to which "metabolic trafficking" of la ctate might occur during brain function is unknown. In this review, the pot ential for an astrocytic-neuronal lactate flux has been estimated by compar ing rates of glucose utilization in brain and in cultured neurons and astro cytes with those for lactate release and uptake. Working brain tissue and i solated brain cells release large amounts of lactate. Cellular lactate upta ke occurs by carrier-mediated facilitated diffusion and is normally limited by its dependence on metabolism of accumulated lactate to maintain a conce ntration gradient. The rate of this process is similar in cultured astrocyt es and glutamatergic neurons, and, at physiologically occurring lactate con centrations, lactate uptake corresponds at most to 25% of the rate of gluco se oxidation, which accordingly is the upper limit for "metabolic trafficki ng" of lactate. Because of a larger local release than uptake of lactate an d the necessity for rapid lactate clearance to maintain the intracellular r edox state to support lactate production in the presence of normal oxygen l evels, brain activation in vivo is probably, in many cases, accompanied by a substantial overflow of glycolytically generated lactate, both to differe nt brain areas and under some conditions (spreading depression, hyperammone mia) to circulating blood. (C) 2001 Wiley-Liss, Inc.