It has been generally believed that the brains energy demands are normally met by the consumption of oxygen and glucose in stoichiometric amounts for the complete oxidation of glucose to oxygen and water. This belief was recently challenged on the basis of results of published PET studies suggesting that more glucose is used than can be accounted for by oxygen consumption during sensory stimulation. These reports provoked a popular but speculative belief that functional activity in brain is supported only by by energy derived from glycolysis and not from oxidative metabolism. Under conditions of limited oxygen supply, this would be expected, but for this to happen in the presence of adequate oxygen violates traditional concepts of energy metabolism. We, therefore, examined in conscious rats in vivo the brains metabolism of [14C]glucose under conditions in which glucose consumption was increased by functional activation. Cerebral arteriovenous O2, glucose, and lactate differences and total and 14C-labeled levels of lactate, glycogen, and glucose in the brain at the end of the period for each functional state were measured. 14C- 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 and unexpected finding. During and following sensory stimulation lactate accumulation in the brain and loss to the blood were much smaller even though the oxygen/glucose uptake ratio was reduced, indicating that glucose utilization exceeded the stoichiometric equivalent of the oxygen consumption during the stimulation period. Also, brain levels of glycogen, which is localized mainly in astroglial cells, was diminished during sensory functional activation. During recovery from the sensory stimulation, however, the oxygen/glucose ratio rose to much higher levels that that for complete stoichiometry, indicating greater oxygen consumption than equivalent glucose utilization. These results, therefore, show that it is not true that functional activaty depends only on glycolytic and not oxidative metabolism. The apparent uncoupling between oxygen and glucose metabolism is only temporal and temporary; the excess glucose utilization leads to accumulation of glucose metabolites in intermediate pools during functional activation which are then oxidized further to carbon dioxide ands water over an extended period of time during recovery. Manuscripts on this work have been published or are in press. This project is now discontinued because the professional staff members who were working on it have left the laboratory and are now continuing these studies at their new locations. PublicationsMadsen, P. L., Cruz, N. F., Sokoloff, L., and Dienel, G. A. 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 lactateefflux from or accumulation in brain tissue. J. Cereb. Blood Flow Metab. 19:393-400; 1999. - local cerebral blood flow oxygen consumption adenosine receptors
| 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 |
| 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 |
