Brain Lactate Metabolism: The Discoveries and the Controversies

• Published in: Journal of cerebral blood flow and metabolism Vol. 32; no. 7; pp. 1107 - 1138
• Main Author: Dienel, Gerald A
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.07.2012; Nature Publishing Group; Sage Publications Ltd
• Subjects: Animals; Astrocytes; Biological and medical sciences; Brain; Brain - metabolism; Cell culture; Cerebral blood flow; Data processing; Energy Metabolism - physiology; Fuels; Glucose; Glucose transport; Glutamic acid; Glycolysis; Humans; Investigative techniques, diagnostic techniques (general aspects); Lactic acid; Lactic Acid - metabolism; Medical sciences; Metabolism; Nervous system; Neurology; Neurons; Neurotransmission; Physical training; Respiration; Review; Signal transduction; Synaptosomes; Ultrasonic investigative techniques; Vascular diseases and vascular malformations of the nervous system; Wastes; neuron; brain activation; glucose; metabolism; astrocyte; lactate shuttling; Nervous system diseases; Astrocyte; Glucose; Metabolism; Cerebral disorder; Encephalon; Lactates; Central nervous system disease; Lactic acid; Cerebrovascular disease
• ISSN: 0271-678X; 1559-7016; 1559-7016
• DOI: 10.1038/jcbfm.2011.175

Potential roles for lactate in the energetics of brain activation have changed radically during the past three decades, shifting from waste product to supplemental fuel and signaling molecule. Current models for lactate transport and metabolism involving cellular responses to excitatory neurotransmission are highly debated, owing, in part, to discordant results obtained in different experimental systems and conditions. Major conclusions drawn from tabular data summarizing results obtained in many laboratories are as follows: Glutamate-stimulated glycolysis is not an inherent property of all astrocyte cultures. Synaptosomes from the adult brain and many preparations of cultured neurons have high capacities to increase glucose transport, glycolysis, and glucose-supported respiration, and pathway rates are stimulated by glutamate and compounds that enhance metabolic demand. Lactate accumulation in activated tissue is a minor fraction of glucose metabolized and does not reflect pathway fluxes. Brain activation in subjects with low plasma lactate causes outward, brain-to-blood lactate gradients, and lactate is quickly released in substantial amounts. Lactate utilization by the adult brain increases during lactate infusions and strenuous exercise that markedly increase blood lactate levels. Lactate can be an ‘opportunistic’, glucose-sparing substrate when present in high amounts, but most evidence supports glucose as the major fuel for normal, activated brain.