Energy Substrates for Neurons during Neural Activity: A Critical Review of the Astrocyte-Neuron Lactate Shuttle Hypothesis
Abstract
PART I: COMPARISON OF GLUCOSE AND LACTATE AS ENERGY SUBSTRATES FOR NEURONS DURING ACTIVITY
Availability of glucose and lactate to neurons during activity
Responses of glycolytic enzymes and LDH to increases in energy demand during neural activity
Suppression of lactate oxidation by increased glycolysis
Thermodynamics of glucose oxidation and lactate oxidation
Glycolysis as an essential energy source for localized areas of brain cells
Maintenance of the cytoplasmic oxidation/reduction balance
The LDH isoform distribution
Distribution of monocarboxylate transporters in neurons and astrocytes
SUMMARY
PART II: EXPERIMENTAL EVIDENCE REGARDING GLUCOSE AND LACTATE USE
Sites of glucose uptake
1:1 coupling of oxidative glucose consumption to glutamate cycling
Uptake of 2-deoxyglucose
Consumption of glucose in cultured neurons and astrocytes
Sites of lactate release
Lactate release from cultured neurons and astrocytes
Lactate release during neural activity in vivo
Sites of lactate use
Comparison of lactate use in neuronal and astrocyte cultures
Sites of lactate use in vivo
Evidence for an astrocyte-neuron lactate shuttle during normal neural activity
Substrate use in an isolated retinal preparation
Exchange of lactate between astrocytes and neurons in coculture systems
Breakdown of glycogen in astrocytes as a source of lactate for neighboring cells
Distributions of carbonic anhydrase and the sodium-bicarbonate transporter
Comparison of glucose and lactate as substrates in the brain and brain tissue
Changes in extracellular glucose and lactate levels in vivo
Changes in brain lactate levels in vivo, as measured with magnetic resonance spectroscopy
Inhibition of glucose consumption by lactate in brain cells in vitro
Comparison of the abilities of glucose and lactate to support neural function in brain slices
Summary
PART III: ROLE OF LACTATE AS AN ENERGY SUBSTRATE
CONCLUSION
Acknowledgments
Footnote
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This article was published in Journal of Cerebral Blood Flow & Metabolism.
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