The traditional concept of a dynamic balance and stoichiometry between oxygen consumption and glucose utilization to meet the brain's energy demands to support its functional activity has been questioned because of recent studies reporting that glucose utilization is stoichiometrically in excess of oxygen consumption during and following cognitive challenges or sensory stimulation. It is now a common speculation that glycolysis is preferentially stimulated to support functional activity in brain and that oxidative metabolism is little, if at all affected. Increased channeling of glucose into non-oxidative pathways when the demand for energy is increased, while the oxygen supply is adequate, violates traditional concepts about energy metabolism. We have, therefore, examined in vivo the metabolism of [14C]glucose in rat brain when glucose consumption was increased by functional activation. We have found that labeling of the brain lactate pool was increased 3- fold during K+-stimulated metabolic activity. About 20% of the glucose taken up by brain was lost to the blood as lactate, and similar quantities must have been transported from activated tissue to other brain regions. Thus, trafficking of intermediary metabolites within the brain can be extensive, a new, unexpected finding. On the other hand, during and after sensory stimulation lactate accumulation and efflux to blood was much smaller even though the oxygen/glucose uptake ratio was reduced, indicating stoichiometrically higher glucose utilization than oxygen consumption. We found, however, that glycogen, which is localized mainly in glial cells, is depleted by sensory functional activation, indicating that some, if not all, of the excess glucose utilization that persists following the functional activation can be explained by the diversion of glucose carbon to the replenishment of metabolic pools depleted by the energy demands of the functional and metabolic activations.
| Sokoloff, L (1999) Energetics of functional activation in neural tissues. Neurochem Res 24:321-9 |
| Nakao, Y; Gotoh, J; Kuang, T Y et al. (1999) Cerebral blood flow responses to somatosensory stimulation are unaffected by scopolamine in unanesthetized rat. J Pharmacol Exp Ther 290:929-34 |
| Eintrei, C; Sokoloff, L; Smith, C B (1999) Effects of diazepam and ketamine administered individually or in combination on regional rates of glucose utilization in rat brain. Br J Anaesth 82:596-602 |
| Elman, I; Sokoloff, L; Adler, C M et al. (1999) The effects of pharmacological doses of 2-deoxyglucose on cerebral blood flow in healthy volunteers. Brain Res 815:243-9 |
| Madsen, P L; Cruz, N F; Sokoloff, L et al. (1999) Cerebral oxygen/glucose ratio is low during sensory stimulation and rises above normal during recovery: excess glucose consumption during stimulation is not accounted for by lactate efflux from or accumulation in brain tissue. J Cereb Blood Flow Metab 19:393-400 |
