Glucose is Necessary to Maintain Neurotransmitter Homeostasis during Synaptic Activity in Cultured Glutamatergic Neurons
- 1 February 2006
- journal article
- Published by SAGE Publications in Journal of Cerebral Blood Flow & Metabolism
- Vol. 26 (10), 1285-1297
- https://doi.org/10.1038/sj.jcbfm.9600281
Abstract
Glucose is the primary energy substrate for the adult mammalian brain. However, lactate produced within the brain might be able to serve this purpose in neurons. In the present study, the relative significance of glucose and lactate as substrates to maintain neurotransmitter homeostasis was investigated. Cultured cerebellar (primarily glutamatergic) neurons were superfused in medium containing [U-13C]glucose (2.5 mmol/L) and lactate (1 or 5 mmol/L) or glucose (2.5 mmol/L) and [U-13C]lactate (1 mmol/L), and exposed to pulses of N-methyl-D-aspartate (300 μmol/L), leading to synaptic activity including vesicular release. The incorporation of 13C label into intracellular lactate, alanine, succinate, glutamate, and aspartate was determined by mass spectrometry. The metabolism of [U-13C]lactate under non-depolarizing conditions was high compared with that of [U-13C]glucose; however, it decreased significantly during induced depolarization. In contrast, at both concentrations of extracellular lactate, the metabolism of [U-13C]glucose was increased during neuronal depolarization. The role of glucose and lactate as energy substrates during vesicular release as well as transporter-mediated influx and efflux of glutamate was examined using preloaded D-[3H]aspartate as a glutamate tracer and DL-threo-β-benzyloxyaspartate to inhibit glutamate transporters. The results suggest that glucose is essential to prevent depolarization-induced reversal of the transporter (efflux), whereas vesicular release was unaffected by the choice of substrate. In conclusion, the present study shows that glucose is a necessary substrate to maintain neurotransmitter homeostasis during synaptic activity and that synaptic activity does not induce an upregulation of lactate metabolism in glutamatergic neurons.Keywords
This publication has 61 references indexed in Scilit:
- A Preferential Role for Glycolysis in Preventing the Anoxic Depolarization of Rat Hippocampal Area CA1 Pyramidal CellsJournal of Neuroscience, 2005
- Compartmentation of glycolysis and glycogenolysis in the perfused rat heartNMR in Biomedicine, 2004
- Role of astrocytes in depolarization-coupled release of glutamate in cerebellar cultures.Neurochemical Research, 2004
- Lactate is a Preferential Oxidative Energy Substrate over Glucose for Neurons in CultureJournal of Cerebral Blood Flow & Metabolism, 2003
- Characterization of depolarization-coupled release of glutamate from cultured mouse cerebellar granule cells using dl-threo-β-benzyloxyaspartate (DL-TBOA) to distinguish between the vesicular and cytoplasmic poolsNeurochemistry International, 2003
- Striking Differences in Glucose and Lactate Levels between Brain Extracellular Fluid and Plasma in Conscious Human Subjects: Effects of Hyperglycemia and HypoglycemiaJournal of Cerebral Blood Flow & Metabolism, 2002
- Immunogold cytochemistry identifies specialized membrane domains for monocarboxylate transport in the central nervous system.Neurochemical Research, 2002
- An Energy Budget for Signaling in the Grey Matter of the BrainJournal of Cerebral Blood Flow & Metabolism, 2001
- Selective Distribution of Lactate Dehydrogenase Isoenzymes in Neurons and Astrocytes of Human BrainJournal of Cerebral Blood Flow & Metabolism, 1996
- 3H-D-aspartate release from cerebellar granule neurons is differentially regulated by glutamate- and K+-stimulationJournal of Neuroscience Research, 1992