<i>In Vivo</i>Evidence for Lactate as a Neuronal Energy Source

Wyss, Matthias T.; Jolivet, Renaud; Buck, Alfred; Magistretti, Pierre J.; Weber, Bruno

doi:10.1523/jneurosci.0415-11.2011

Cited by 366 publications

(305 citation statements)

References 56 publications

(67 reference statements)

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“…astrocytes in the mammalian brain. Astrocytes, which are highly glycolytic, have been shown to export lactate which is taken up by neurons for energy production, a mechanism coined "Astrocyte to Neuron Lactate Shuttle" (ANLS; [45][46][47][48]. Moreover, it has been suggested, that astrocytes could also take up lactate, dependent on the concentration gradient (49).…”

Section: Discussionmentioning

confidence: 99%

Intracellular and Extracellular Carbonic Anhydrases Cooperate Non-enzymatically to Enhance Activity of Monocarboxylate Transporters

Klier

Andes

Deitmer

et al. 2014

Journal of Biological Chemistry

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Background: Monocarboxylate transporters (MCTs) mediate the shuttling of high-energy metabolites between different cells. Results: Transport activity of MCTs is augmented by intracellular and extracellular carbonic anhydrases (CAs). Conclusion: Intracellular and extracellular CAs can work in concert to ensure rapid shuttling of metabolites across the cell membrane. Significance: CAs play a pivotal role as regulators of metabolite transport in different tissues.

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Section: Discussionmentioning

confidence: 99%

Intracellular and Extracellular Carbonic Anhydrases Cooperate Non-enzymatically to Enhance Activity of Monocarboxylate Transporters

Klier

Andes

Deitmer

et al. 2014

Journal of Biological Chemistry

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“…Brain lactate metabolism GA Dienel Lactate infusion increase plasma level from 1.3±0.6 to 5.8±1.6 mmol/L Reduced glucose utilization in anesthetized rat by a mean of 38%, in dose-dependent manner Wyss et al, 2011 Running wheel exercise at 85% of maximal O 2 uptake…”

Section: Glucose-sparing Action Of Alternative Substrates That Increamentioning

confidence: 99%

Brain Lactate Metabolism: The Discoveries and the Controversies

Dienel

2011

J Cereb Blood Flow Metab

416

434

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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-toblood 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. Keywords: astrocyte; brain activation; glucose; lactate shuttling; metabolism; neuron Glucose is the major fuel for the brain, and its metabolism by different pathways has important functions related to energetics, neurotransmission, oxidation-reduction (redox) reactions, and biosynthesis of essential brain components (Figure 1). For many decades, lactate production in the brain was viewed as a consequence of inadequate oxygen delivery, disruption of oxidative metabolism, or mismatch between glycolytic and oxidative rates (Siesjö, 1978), but more recently, the conceptual role of lactate metabolism and function in the normal brain have undergone major changes, shifting from developmental fuel and glycolytic waste product to include its use as a supplemental fuel and signaling molecule. Starting in the 1970s to 1980s studies carried out in different laboratories with diverse experimental interests related to brain function brought attention to upregulation of glycolysis, lactate production, lactate release into the blood, the possibility of lactate shuttling among cell types within the brain, lactate fueling adult brain during exercise, and roles of lactate in the regulation of blood flow; some of these topics are controversial and highly debated. The experimental paradigm and physiologic status of subjects are critical for interpretation of data, and this review first presents a brief historical overview of studies related to brain lactate transport and metabolism, then compares sets of data to provide a perspective and context within which the consistency of simi...

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“…However, a recent study by Wyss et al (2011) also using electrical stimulation of the infraorbital branch of the trigeminal nerve with almost identical parameters of stimulation in rats demonstrated that Lac is indeed used at an increased rate by the brain to maintain neuronal activity. In addition, we also found an increase of lactate to a new steady state in agreement with studies by Mangia et al in the human visual cortex.…”

Section: Functional Magnetic Resonance Spectroscopy During Sustained mentioning

confidence: 99%

Characterization of sustained BOLD activation in the rat barrel cortex and neurochemical consequences

Just¹,

Xin²,

Frenkel³

et al. 2013

NeuroImage

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To date, only a couple of functional MR spectroscopy (fMRS) studies were conducted in rats. Due to the low temporal resolution of 1 H MRS techniques, prolonged stimulation paradigms are necessary for investigating the metabolic outcome in the rat brain during functional challenge. However, sustained activation of cortical areas is usually difficult to obtain due to neural adaptation. Anesthesia, habituation, high variability of the basal state metabolite concentrations as well as low concentrations of the metabolites of interest such as lactate (Lac), glucose (Glc) or γ-aminobutyric acid (GABA) and small expected changes of metabolite concentrations need to be addressed. In the present study, the rat barrel cortex was reliably and reproducibly activated through sustained trigeminal nerve (TGN) stimulation. In addition, TGN stimulation induced significant positive changes in lactate (+1.01 μmol/g, p b 0.008) and glutamate (+0.92 μmol/g, p b 0.02) and significant negative aspartate changes (−0.63 μmol/g, p b 0.004) using functional 1 H MRS at 9.4 T in agreement with previous changes observed in human fMRS studies. Finally, for the first time, the dynamics of lactate, glucose, aspartate and glutamate concentrations during sustained somatosensory activation in rats using fMRS were assessed. These results allow demonstrating the feasibility of fMRS measurements during prolonged barrel cortex activation in rats.

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In VivoEvidence for Lactate as a Neuronal Energy Source

Cited by 366 publications

References 56 publications

Intracellular and Extracellular Carbonic Anhydrases Cooperate Non-enzymatically to Enhance Activity of Monocarboxylate Transporters

Intracellular and Extracellular Carbonic Anhydrases Cooperate Non-enzymatically to Enhance Activity of Monocarboxylate Transporters

Brain Lactate Metabolism: The Discoveries and the Controversies

Characterization of sustained BOLD activation in the rat barrel cortex and neurochemical consequences

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