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Keywords:

  • glucose;
  • lactate;
  • glutamate;
  • brain metabolism;
  • metabolite trafficking;
  • astrocytes;
  • neurons

Abstract

The dependence of brain function on blood glucose as a fuel does not exclude the possibility that lactate within the brain might be transferred between 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 glycolytically derived energy for Na+-dependent accumulation of transmitter glutamate and its amidation to glutamine, and 2) the generated lactate is quantitatively transferred to neurons for oxidative degradation. However, astrocytic glutamate uptake can be fuelled by either glycolytically or oxidatively derived energy, and the extent to which “metabolic trafficking” of lactate might occur during brain function is unknown. In this review, the potential for an astrocytic–neuronal lactate flux has been estimated by comparing rates of glucose utilization in brain and in cultured neurons and astrocytes with those for lactate release and uptake. Working brain tissue and isolated brain cells release large amounts of lactate. Cellular lactate uptake occurs by carrier-mediated facilitated diffusion and is normally limited by its dependence on metabolism of accumulated lactate to maintain a concentration gradient. The rate of this process is similar in cultured astrocytes and glutamatergic neurons, and, at physiologically occurring lactate concentrations, lactate uptake corresponds at most to 25% of the rate of glucose oxidation, which accordingly is the upper limit for “metabolic trafficking” of lactate. Because of a larger local release than uptake of lactate and the necessity for rapid lactate clearance to maintain the intracellular redox state to support lactate production in the presence of normal oxygen levels, brain activation in vivo is probably, in many cases, accompanied by a substantial overflow of glycolytically generated lactate, both to different brain areas and under some conditions (spreading depression, hyperammonemia) to circulating blood. © 2001 Wiley-Liss, Inc.