Is there uncoupling of oxygen and glucose utilization during neuronal activation?

F. Orzi, M. Rasura, C. Fieschi, F. Fornai

Research output: Contribution to journalArticlepeer-review

Abstract

The brain utilizes oxygen and glucose in almost stoichiometric amounts under physiological conditions. Conventional knowledge suggests that the O2/glucose utilization ratio is kept close to 6 not only at rest but also under physiological stimulation. A number of different stimuli, however, seem to cause a disproportionately higher increase in blood flow and glucose utilization than in oxygen consumption, suggesting that the brain utilizes anaerobic glycolysis, instead of oxidative glucose metabolism, in order to meet the energy requirements associated with functional neuronal stimulation. Accordingly, measurement of extracellular lactate levels has been proposed as a means for detecting functional changes within discrete brain areas, in freely moving animals. The issue is under study. In this study we sought to compare rates of glucose utilization, as measured by the [14C]2-deoxyglucose method, and concentrations of extracellular lactate, as detected by in vivo microdialysis, in defined brain areas of freely-moving rats exposed to odorants. The olfactory stimulation by evoking complex behavioral changes was expected to markedly enhance the cerebral functional activity. The measurements were carried out in Sprague-Dawley rats (250-300 g). Animals were split into 3 groups: one group (n = 4) was exposed to a solution of pheromone; a second group (n = 4) to a conventional odorant. The third group was exposed to saline and served as control. The animals of each group were used either for measuring local cerebral glucose utilization or brain tissue lactate content. Both measurements were carried out in freely moving animals under comparable experimental conditions. The study shows that presenting the animals with either a conventional odorant or with pheromone causes a marked increase in the extracellular lactate levels within defined brain areas of the freely moving rat. The very same stimuli produced no change in glucose utilization as measured by the [14C]2-deoxyglucose method. The increased tissue content of lactate reflects increased local anaerobic glycolysis, as the blood-brain barrier is essentially impermeable to the lactate in the blood. Our experimental setting, therefore, provided us with an example of a physiological condition characterized by a dramatic, apparent uncoupling between oxygen and glucose utilization. We speculate that the discrepancy is more apparent than substantial. In fact, it probably reflects the different temporal profiles of the changes of the two parameters measured in this study.

Original languageEnglish
JournalNeurological Sciences
Volume21
Issue number4 SUPPL.
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

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