• Corpus ID: 202659840

Astrocyte-Neuron Metabolic Pathways

  title={Astrocyte-Neuron Metabolic Pathways},
  author={Luc Pellerin and Giovanni Pellegri and Philippe G. Bittar and Yves Charnay and Constantin Bouras and Jean-Luc Martin and Nephi Stella and Pierre Julius Magistretti},
Mounting evidence from in vitro experiments indicates that lactate is an efficient energy substrate for neurons and that it may significantly contribute to maintain synaptic transmission, particularly during periods of intense activity. Since lactate does not cross the blood-brain barrier easily, blood-borne lactate cannot be a significant source. In vitro studies by several laboratories indicate that astrocytes release large amounts of lactate. In 1994, we proposed a mechanism whereby lactate… 

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Selective Distribution of Lactate Dehydrogenase Isoenzymes in Neurons and Astrocytes of Human Brain
In vivo data suggest that lactate may be formed in certain cells and oxidized in others, and the production and characterization of two rat antisera, specific for the LDH-5 andLDH-1 subunits of lactate dehydrogenase, respectively support the notion of a regulated lactate flux between astrocytes and neurons.
Excitatory amino acids stimulate aerobic glycolysis in astrocytes via an activation of the Na+/K+ ATPase.
The pharmacological characteristics and molecular mechanisms of this action, which involve a massive influx of Na+ as a result of the cotransport of the amino acid with Na+, by Na(+)-dependent transporters and a subsequent activation of the Na+/K+ ATPase, reveal a simple mechanism for coupling neuronal activity to glucose utilization.
Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization.
  • L. Pellerin, P. Magistretti
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1994
It is reported that glutamate, in addition to its receptor-mediated actions on neuronal excitability, stimulates glycolysis--i.e., glucose utilization and lactate production--in astrocytes and is consistent with data obtained from functional brain imaging studies indicating local nonoxidative glucose utilization during physiological activation.
Regulation of energy metabolism in synaptic terminals and cultured rat brain astrocytes: differences revealed using aminooxyacetate.
The findings demonstrate that inhibiting transamination with AOAA had very different effects on the oxidation of energy substrates in the two preparations, suggesting that the regulation of metabolism is quite different in astrocytes and synaptic terminals.
Endogenous Monocarboxylates Sustain Hippocampal Synaptic Function and Morphological Integrity during Energy Deprivation
Results suggest that endogenous monocarboxylates rather than glucose maintain neuronal integrity during energy deprivation, and EPSPs supported by 2–3.3 mm glucose were sensitive to 4-CIN, suggesting that endogenousMonocar boxylates are involved in maintaining neuronal function even under conditions of mild glucose deprivation.
Comparison of Lactate Transport in Astroglial Cells and Monocarboxylate Transporter 1 (MCT 1) Expressing Xenopus laevis Oocytes
Comparison of lactate transport in MCT1 expressing oocytes with lactate Transport in glial cells revealed that MCT 1 can account for all characteristics of lactates transport inglial cells, providing further molecular support for the existence of a lactate shuttle between astrocytes and neurons.
Expression of the monocarboxylate transporter MCT2 by rat brain glia
Light microscopic immunocytochemistry indicated that the MCT2 transporter was abundant in glial limiting membranes, ependymocytes, and neuropil, particularly in the lacunosum molecular layer of hippocampus and the molecular layers of cerebellum, lending support to the concept that astrocytes play a significant role in cerebral energy metabolism by transporting lactate and other monocarboxylates.
Expression of monocarboxylate transporter mRNAs in mouse brain: support for a distinct role of lactate as an energy substrate for the neonatal vs. adult brain.
The notion that monocarboxylates are important energy substrates for the brain at early postnatal stages is supported and the observation of a sustained intraparenchymal expression of monocareboxylate transporter mRNAs in adults reinforces the view that an intercellular exchange of lactate occurs within the adult brain.
Lactate-supported synaptic function in the rat hippocampal slice preparation.
Under conditions that lead to lactate accumulation (cerebral ischemia), this "end product" may be a useful alternative as a substrate for energy metabolism.
Lactate released by Muller glial cells is metabolized by photoreceptors from mammalian retina
It is proposed that net production and release of lactate by Muller cells serves to maintain their glycolysis elevated and to fuel mitochondrial oxidative metabolism and glutamate resynthesis in photoreceptors.