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Cited by 467Neuroscience and Neuropharmacology ResearchCancer, Hypoxia, and MetabolismNeurogenesis and neuroplasticity mechanisms

Neuronal Stimulation Triggers Neuronal Glycolysis and Not Lactate Uptake

Open access
Díaz-García, Carlos Manlio, Mongeon, Rebecca, Lahmann, Carolina, Koveal, Dorothy, Zucker, Hannah, Yellen, Gary·2017·Cell Metabolism
DOI 10.1016/j.cmet.2017.06.021PMC PMC5559896
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Abstract

SUMMARY Proper brain function requires a substantial energy supply, up to 20% of whole body energy in humans, and brain activation produces large dynamic variations in energy demand. While local increases in cerebral blood flow are well known, the cellular responses to energy demand are controversial. During brain excitation, glycolysis of glucose to lactate temporarily exceeds the rate of mitochondrial fuel oxidation; although the increased energy demand occurs mainly within neurons, some have suggested this glycolysis occurs mainly in astrocytes, which then shuttle lactate to neurons as their primary fuel. Using metabolic biosensors in acute hippocampal slices and brains of awake mice, we find that neuronal metabolic responses to stimulation do not depend on astrocytic stimulation by glutamate release, nor do they require neuronal uptake of lactate; instead they reflect increased direct glucose consumption by neurons. Neuronal glycolysis temporarily outstrips oxidative metabolism, and provides a rapid response to increased energy demand.

AI snapshot

Written from the paper’s full text.

TL;DR

Using genetically encoded metabolic biosensors in acute hippocampal slices and awake mouse cortex, this paper finds that neuronal stimulation raises cytosolic NADH:NAD+ via increased neuronal glycolysis, not via astrocyte-derived lactate uptake. The results contradict a stimulation-dependent astrocyte-neuron lactate shuttle and support direct neuronal glucose consumption as a rapid metabolic response.

Key findings

  • Synaptic stimulation of dentate granule neurons produced a ~2-fold rise in cytosolic NADH:NAD+ (Peredox lifetime 1.73 ± 0.01 ns at baseline to 1.88 ± 0.01 ns stimulated; mean ± SEM, n=166 neurons), lasting about 3 minutes and correlating with Ca2+ responses.
  • Blocking postsynaptic glutamate receptors abolished the neuronal NADH transient, and antidromic stimulation still produced similar transients, indicating glutamate stimulation of astrocytes is neither sufficient nor necessary.
  • MCT inhibition with AR-C155858 reduced the neuronal response to exogenous lactate to 27% ± 2% of control (n=36 neurons) but did not abolish—and actually increased—the stimulation-induced NADH transient (95% CI 1.23- to 1.34-fold larger). LDH inhibition reduced exogenous lactate responses by 78% ± 3% but increased stimulation-induced NADH transients by 37% ± 5% (n=54 neurons).
  • In awake mice, whisker stimulation produced ~4–5 minute NADH transients in responsive S1-BF neurons, with a smaller typical increase (~33% over resting); MCT inhibition reduced exogenous lactate responses by 85.3% ± 6.3% (n=59 neurons in 6 animals) but did not diminish whisker-stimulation NADH transients.
  • Neuronal intracellular glucose showed stimulation-induced dips that became larger with partial glucose transport inhibition and were reduced by MCT inhibition; glycolysis inhibition with iodoacetic acid greatly reduced NADH transients.

Methods

  • Acute mouse hippocampal slices and awake, unanesthetized mice with cranial windows; C57BL/6NCrl mice, including postnatal day 1 viral injections for hippocampal sensors and adult mice for cortical imaging.
  • Two-photon fluorescence lifetime imaging of genetically encoded biosensors: Peredox for cytosolic NADH:NAD+, RCaMP1h for Ca2+, SweetieTS for glucose, Laconic for lactate, and pHRed for pH.
  • Stimulation via electrical synaptic or antidromic stimulation in slices and 10-second 5 Hz whisker stimulation in vivo; pharmacology included NBQX/D-AP5, AR-C155858, GSK-2837808A, iodoacetic acid, cytochalasin B, and aminooxyacetate.

Limitations

  • The paper states that because experiments used optical signals from neuronal cell bodies, it cannot exclude ANLS activity at synaptic terminals; it also cannot exclude some contribution of mitochondrial NADH shuttles to the NADH transients.
  • The paper states that the relative contributions of glycolysis and oxidative phosphorylation to immediate neuronal energy demands remain unknown.
  • The text notes technical caveats: Laconic has shallow lactate dependence and pH sensitivity, producing uncertainty in absolute lactate concentrations; AOA’s small effect could partly reflect alanine transaminase inhibition; and in vivo drug delivery through the permeable window required higher concentrations and longer times than in slices.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.cmet.2017.06.021

Cites

68 of 68 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 35 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Stimulation-induced NADHCYT transients occur in vivo in awake mice with whisker stimulation.

    “Stimulation-induced transients in NADHCYT were not unique to the in vitro hippocampal slice preparation, but were also observed in a more natural in vivo situation, in the brains of awake, unanesthetized mice.”
    Quote in the paperSubstantial claim
  • Findingown data

    In vivo NADHCYT transients are well-correlated with Ca2+ response even for small responses.

    “As for the in vitro case, the size of the NADHCYT transients was well-correlated with the Ca2+ response even for small responses (Figure 7C).”
    Quote in the paperNot a substantial claim
  • Findingown data

    MCT inhibitor inhibits stimulation-induced glucose dips.

    “Indeed, we found that application of MCT inhibitor to the slice did inhibit the stimulation-induced dips reported by the glucose sensor (Fig 5C, D).”
    Quote in the paperSubstantial claim
  • Findingown data

    Ca2+ and NADHCYT responses are well-correlated even for the smallest responses.

    “Recording from many neurons, we observed a wide range of both Ca2+ and NADHCYT responses, but the two were well-correlated even for the smallest responses (Fig. 1D)”
    Quote in the paperNot a substantial claim
  • Findingown data

    AOA causes only a small reduction (~10%) in stimulation-induced NADHCYT transients.

    “There was only a small reduction (~10%) in the transients in the presence of AOA, relative to the slight increase in parallel controls with pyruvate (Fig. 6C, Suppl. Fig. S6).”
    Quote in the paperSubstantial claim
  • May combine two claims. 18
  • Classified as probably not a substantial claim. 15

  • May combine two claims.

    Findingown data

    Blockade of postsynaptic ionotropic glutamate receptors abolishes the NADHCYT transient while glutamate release and mGluR signaling remain intact.

    “The opposite was seen: blockade of the postsynaptic response (as judged from the disappearance of the postsynaptic Ca2+ transient, and the disappearance of the EPSP from an extracellular electrode; Fig 2A, B and Suppl. Fig. S3) was accompanied by disappearance of the NADHCYT transient (Fig 2B, C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In vivo, responsive neurons show ~4-5 min elevation in NADHCYT; non-responsive neurons show no significant change.

    “Practically all of these responsive neurons exhibited an approximately 4–5 minute long elevation in NADHCYT (Figure 7A, B), while neighboring non-responsive neurons showed no significant change.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In vivo, MCT inhibitor reduces lactate-induced NADHCYT increase by 85.3% ± 6.3% but does not diminish whisker stimulation-induced NADHCYT transients.

    “Application of the MCT inhibitor AR-C155858 (at 50 μM rather than the 2 μM used for slice) effectively reduced the size of the lactate-induced increase (by 85.3% ± 6.3%, mean ± SEM, n=59 neurons in 6 animals; Fig. 7D). Nevertheless, neuronal NADHCYT transients induced by whisker stimulation were not diminished by the MCT inhibitor (Fig. 7E, F).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Synaptic stimulation produces small transient drops (dips) in neuronal intracellular [glucose] with similar time course to NADHCYT transients.

    “We observed small transient drops (dips) in neuronal intracellular [glucose] upon synaptic stimulation that had a very similar time course to the NADHCYT transients (Fig. 5A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    LDH inhibitor GSK-2837808A reduces NADHCYT response to exogenous lactate by 78% ± 3% but does not diminish stimulation-induced NADHCYT response; instead it increases it by 37% ± 5%.

    “As expected, application of the LDH inhibitor reduced the NADHCYT response to direct application of exogenous lactate (by 78% ± 3% of the original response, mean ± SEM, n=54 neurons; Fig. 3E).”
    • Also stated in: § Lactate import does not contribute to neuronal NADHCYT transients · plain
      “Instead, the stimulation-induced NADHCYT responses were larger (by 37% ± 5%; n=54 neurons; Fig. 3F), as expected for production of NADH within the neuron when LDH-dependent recycling to NAD+ is inhibited.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The LDH inhibitor GSK-2837808A specifically inhibits lactate dehydrogenase.

  • May combine two claims.

    Findingown data

    Partial inhibition of glucose transport with cytochalasin B lowers baseline [glucose]i but increases the size of stimulation-induced glucose dips.

    “When we deliberately reduced glucose transport rate chronically, by partial inhibition with cytochalasin B, the baseline [glucose]i was predictably lower, but the stimulation-induced dips in [glucose]i actually became larger (Fig 5A, B), consistent with our hypothesis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In dentate granule neurons in hippocampal slice, typical increase in NADH:NAD+ ratio is ~2-fold; in barrel cortex in vivo, ~33% increase.

    “In dentate granule neurons in a hippocampal slice, the typical increase in this ratio is substantial - approximately a 2-fold increase above the resting level. In neurons of barrel cortex observed in vivo, the typical increase is smaller (about a 33% increase over the resting level), but still substantial.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    IAA treatment diminishes baseline NADHCYT and greatly reduces stimulation-induced NADHCYT transient.

    “IAA treatment diminished the baseline (consistent with a contribution of glycolysis to the resting NADHCYT level), and upon return to the experimental temperature, the stimulation-induced NADHCYT transient was much smaller, despite a slightly larger Ca2+ transient in response to stimulation.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The resting brain consumes glucose and metabolizes it nearly completely to CO2.

    “It is generally agreed that the “resting” brain, under normal metabolic circumstances, consumes glucose and metabolizes it nearly completely to CO2 (Clarke and Sokoloff, 1994; Madsen et al., 1999).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Clarke and Sokoloff, 1994

      Not checked in the free run.

    • cites Madsen et al., 1999 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    We cannot exclude ANLS activity at synaptic terminals.

    “Because our experiments were all done with optical signals from the cell bodies of neurons, we cannot exclude the possibility of ANLS activity at synaptic terminals”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Our results support an ANLS that functions at rest but not during neuronal stimulation.

    “Our results support the possibility of an ANLS that functions at rest but not during neuronal stimulation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    In vivo metabolic transients are endogenous to neurons and do not rely on lactate import from extracellular space or astrocytes.

    “The failure of MCT inhibitor to abolish the stimulation-induced transients in vivo supports the conclusion that such metabolic transients are endogenous to the neurons and do not rely on lactate import from the extracellular space or from astrocytes.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationown data

    The physiological coordination of glycolysis and oxidative metabolism may be choreographed by calcium influx.

    “The physiological coordination of both glycolysis and oxidative metabolism in response to neuronal activity may be choreographed by calcium influx, which, as shown in Figs. 1D and 7C, is tightly correlated to the cytosolic NADH transients.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Neurons normally export lactate when their metabolism is activated by stimulation.

    “The fact that the transients are actually larger when the MCTs are inhibited may indicate that neurons normally export lactate when their metabolism is activated by stimulation, as discussed below.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    NADHCYT can rise in response to increased glycolysis, increased conversion of lactate to pyruvate, or decreased activity of mitochondrial NADH shuttles.

    “NADHCYT can rise in response to either increased glycolysis (which converts NAD+ to NADH at the GAPDH step), to increased conversion of lactate to pyruvate, or to decreased activity of mitochondrial NADH shuttles.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Mice were randomly allocated to experimental groups.

    “Wild-type C57BL/6NCrl mice of both genders were bred in house and used in all acute brain slice and in vivo experiments, and mice were randomly allocated to experimental groups.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    RCaMP1h expression alone led to some signal in the green optical channel, probably due to an immature fluorophore, in direct experiments approximately 4.4% of the red fluorescence intensity, and having a lifetime of ~0.71 ns; these values were used to correct the baseline in dual expression experiments.

    “Similarly, RCaMP1h expression alone led to some signal in the green optical channel, probably due to an immature fluorophore, in direct experiments approximately 4.4% of the red fluorescence intensity, and having a lifetime of ~0.71 ns; these values were used to correct the baseline in dual expression experiments.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    When imaging from the same cortical region on multiple days, previously imaged neurons were re-identified using the pattern of the surface vasculature as guidance, and then an adjacent volume was selected to ensure that all neurons in the sample were unique.

    “When imaging from the same cortical region on multiple days, previously imaged neurons were re-identified using the pattern of the surface vasculature as guidance, and then an adjacent volume was selected to ensure that all neurons in the sample were unique.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationreasoning

    Like muscle, the brain has no doubt evolved to meet the large instant-to-instant changes in energy demands with a choreographed regulation of the core metabolic pathways, to ensure not only brain cell health but organismal survival.

    “Like muscle, the brain has no doubt evolved to meet the large instant-to-instant changes in energy demands with a choreographed regulation of the core metabolic pathways, to ensure not only brain cell health but organismal survival.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Viral expression of Peredox and RCaMP1h permitted recording from different neurons in the same mice on different days.

    “Viral expression of Peredox and RCaMP1h permitted recording from different neurons in the same mice on different days (Andermann et al., 2010; O’Connor et al., 2010).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Andermann et al., 2010

      Not checked in the free run.

    • cites O’Connor et al., 2010

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PET studies show that blood flow and glucose consumption are dramatically increased by brain activation, but oxygen consumption barely increases.

    “PET studies also show that blood flow and glucose consumption are dramatically increased by brain activation, but oxygen consumption barely increases (Fox and Raichle, 1986; Fox et al., 1988).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Fox and Raichle, 1986 source

      Not checked in the free run.

    • cites Fox et al., 1988 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Most likely the changes in free [NADH] are already buffered by high levels of cytosolic dehydrogenases that bind NADH, and the additional expression of sensor makes only a negligible change in the buffering capacity.

    “Most likely the changes in free [NADH] are already buffered by high levels of cytosolic dehydrogenases that bind NADH (Zhang et al., 2002), and the additional expression of sensor makes only a negligible change in the buffering capacity.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Zhang et al., 2002

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    For this reason, we mostly measured the net lifetime change for the transients, relative to baseline (ΔLT).

    “For this reason, we mostly measured the net lifetime change for the transients, relative to baseline (ΔLT).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In the evolution of skeletal muscle, the muscle fibers with the most dynamic energy requirements -- the fast-twitch fibers -- tend to rely on glycolysis for prompt energy production.

    “However, it is known that in the evolution of skeletal muscle, the muscle fibers with the most dynamic energy requirements -- the fast-twitch fibers -- tend to rely on glycolysis for prompt energy production (Crow and Kushmerick, 1982; Spriet, 1989).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Crow and Kushmerick, 1982

      Not checked in the free run.

    • cites Spriet, 1989

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The commonly used MCT inhibitor α-cyano-4-hydroxycinnamate (4-CIN) blocks mitochondrial pyruvate uptake with higher affinity than it blocks MCTs.

    “unlike the commonly used MCT inhibitor α-cyano-4-hydroxycinnamate (4-CIN), which blocks mitochondrial pyruvate uptake with higher affinity than it blocks MCTs (Halestrap and Denton, 1974).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Halestrap and Denton, 1974

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Bleedthrough of green Peredox fluorescence into the red RCaMP optical channel was corrected using the ratio of measured red to green fluorescence observed when only Peredox was expressed, approximately 6.0%.

    “Bleedthrough of green Peredox fluorescence into the red RCaMP optical channel was corrected using the ratio of measured red to green fluorescence observed when only Peredox was expressed (Suppl. Fig. S2), approximately 6.0%.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    The ultimate fate of the exported lactate may be a combination of "catch-up" oxidation by many neighboring brain cells (and by the stimulated neurons themselves) as well as some net lactate excretion from the brain, particularly when activation is strong and synchronous, as in epilepsy.

    “of “catch-up” oxidation by many neighboring brain cells (and by the stimulated neurons themselves) as well as some net lactate excretion from the brain (Dienel, 2012; Glenn et al., 2015), particularly when activation is strong and synchronous, as in epilepsy (Collins et al., 1970; During et al., 1994)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Dienel, 2012 source

      Not checked in the free run.

    • cites Glenn et al., 2015

      Not checked in the free run.

    • cites Collins et al., 1970

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Green glucose sensor fluorescence produced a bleedthrough of ~5.9% to the red channel.

    “Likewise, green glucose sensor fluorescence produced a bleedthrough of ~5.9% to the red channel.”
    Quote in the paperNot a substantial claim
28 of 28

  • The paper relies on this without support.

    The increased energy demand during brain excitation occurs mainly within neurons.

    “although the increased energy demand occurs mainly within neurons, some have suggested this glycolysis occurs mainly in astrocytes”

  • The paper relies on this without support.

    The Peredox biosensor is expressed in the cytosol and not targeted to mitochondria.

    “The biosensor is expressed in cytosol and not targeted to mitochondria; it therefore reports cytosolic NADH: NAD+ ratio.”

  • The paper relies on this without support.

    NADH does not pass through mitochondrial membranes.

    “The NADHCYT transients reported by Peredox are in principle compartmentally separated from the changes in mitochondrial NADH, and NADH does not pass through the mitochondrial membranes.”

  • The paper relies on this without support.

    The LDH inhibitor GSK-2837808A specifically inhibits lactate dehydrogenase.

    “the neuronal NADHCYT transients were elevated rather than abolished upon inhibition of lactate dehydrogenase by the high-affinity inhibitor GSK-2837808A (2 μM; Fig. 3D, F).”

  • The paper relies on this without support.

    Both glycolysis and oxidative metabolism are elevated after stimulation.

    “Despite the fact that both glycolysis and oxidative metabolism are elevated after stimulation”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Previously published data strongly indicate that the increase in lactate and glutamate levels is the consequence of the surge in glycolysis and the ensuing increase of cytosolic NADH:NAD+ ratio taking place during neuronal activation.

    “but previously published data strongly indicate that the increase in lactate and glutamate levels is the consequence of the surge in glycolysis and the ensuing increase of cytosolic NADH:NAD+ ratio taking place during neuronal activation (Díaz-García et al., 2017).”

    From Perception is associated with the brain’s metabolic response to sensory stimulation (2022) · cites this paper as Díaz-García et al., 2017

    The Results and Discussion (page numbers unavailable) link neuronal activation to increased glycolysis and a rise in cytosolic NADH:NAD+, and the Discussion suggests that activated neurons produce and export glycolytic lactate. The paper does not establish that increased glutamate levels are a consequence of glycolysis or the NADH:NAD+ rise; it discusses glutamate release as part of synaptic stimulation instead. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Astrocyte-derived lactate is not required for the bioenergetic response to stimulation in neurons.

    “This is consistent with a recent report that astrocyte-derived lactate is not required for the bioenergetic response to stimulation in neurons (Díaz-García et al., 2017).”

    From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Díaz-García et al., 2017

  • Use of pure lactate as an alternative fuel, rather than a redox-balanced mixture of lactate and pyruvate, abnormally elevates the low cytosolic NADH redox ratio in neurons.

    “However, the use of pure lactate as an alternative fuel, rather than a redox-balanced mixture of lactate and pyruvate, abnormally elevates the low cytosolic NADH redox ratio in neurons (seen in vitro by Hung et al. [2011] and Mongeon et al. [2016] as well as in vivo by Díaz-García et al. [2017]); this decreases the rate of neuronal glycolysis in a way that would not represent the normal effect in”

    From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Díaz-García et al., 2017

  • Inhibition of MCT in vivo in cortical neurons of awake mice blocks the NADHCYT response to exogenous lactate but not to sensory stimulation.

    “Inhibition of MCT in vivo in the cortical neurons of awake mice also blocks the NADHCYT response to exogenous lactate but not to sensory stimulation.”

    From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Díaz-García et al., 2017

  • Blockade of MCT or LDH leads to enhancement of the NADHCYT transients.

    “These blockers instead lead to enhancement of the NADHCYT transients, suggesting that neurons normally export lactate when stimulated.”

    From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Díaz-García et al., 2017

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Related

Authors
Díaz-García, C. M., Mongeon, R., Lahmann, C., Koveal, D., Zucker, H., & Yellen, G.
Affiliations
Harvard University (US)
Corresponding author
Yellen, Gary
ORCID
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2017-08
Volume
26
Issue
2
Pages
361-374.e4
ISSN
1550-4131 (ISSN-L)
DOI
10.1016/j.cmet.2017.06.021
PMC
PMC5559896
OpenAlex
W2739924689
Semantic Scholar
a96cd5dd74379072ec837b55007abc76f4f54521
Cited by
466
References
71
Citations by year
2026: 39 · 2025: 62 · 2024: 50 · 2023: 52 · 2022: 51 · 2021: 62 · 2020: 60 · 2019: 40 · 2018: 42 · 2017: 7 · 2015: 1
FWCI
19.78
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
NIH (R01 NS055031, DP1 EB016985, F32 NS080455, F32 NS093784, F32 NS100331)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
lactate utilization, brain energy metabolism, neurostimulation, astrocytes, glutamate release, glucose utilization, oxidative metabolism, hippocampal slices, brain energy demand
MeSH terms
Animals, Glycolysis, Hippocampus, Male, Neurons, Lactic Acid, Mice

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