Coupling of brain function to metabolism: Evaluation of energy requirements

A. Gjedde

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

There is no rigid association in vivo between changes of oxygen consumption, glucose combustion, and blood flow in the human brain. The claim that cerebral blood flow rises to satisfy the demands for oxygen and glucose during neuronal excitation therefore is simplistic. "<FOR VERIFICATION>Energy budget estimates indicate that most of the cerebral energy demand reflects the steady-state level of graded post-synaptic membrane depolarization, followed by action potential generation and propagation. Increased energy supply is required to maintain the depolarization of neuronal membranes when sodium and potassium conductances are increased."<FOR VERIFICATION>Glucose, pyruvate and lactate occupy single tissue compartments, but transient shifts of the relative activity of neurons and astrocytes disrupt the steady-state, and the properties of lactate dehydrogenase mayy vary temporally, as dictated by transient shifts of cytosolic redox potentials and pH values. Pyruvate and lactate generation invariably occurs when astrocytes are activated by glutamate release. In these cases, the increased demand for glutamate imposes a metabolic rate on astroglial cells that exceeds their modest oxidative capacity. Although the resulting pyruvate and lactate accumulation is influenced by lactate export or import across the blood-brain barrier, pyruvate and lactate accumulate in a joint pool, to which astrocytes produce more pyruvate than neurons. The blood flow increase appears to be coupled to the rate of glycolysis. There is increasing evidence that the putative mechanism underlying the flow-glycolysis couple resides in astrocytes. The evidence suggests that the increase of oxidative metabolism in neurons is coupled to a rise of pyruvate, as dictated by the degree of mitochondrial activation. Under some circumstances, regional 'peaks' of increased blood flow and increased oxygen consumption could be dissociated by the differential activation of primary and secondary neuronal networks. The activations accompanying the most complex processing of information could be those with the tightest coupling between oxygen consumption and blood flow and hence with the least generation of lactate.

Original languageEnglish (US)
Title of host publicationHandbook of Neurochemistry and Molecular Neurobiology
Subtitle of host publicationBrain Energetics. Integration of Molecular and Cellular Processes
PublisherSpringer US
Pages343-400
Number of pages58
ISBN (Print)9780387303468
DOIs
StatePublished - Dec 1 2007

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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