The DOI matches its Crossref record; 68 of the 71 references it cites were found in a registry or an index; none of the 35 sources its claims cite is checked for support yet.
Neuronal Stimulation Triggers Neuronal Glycolysis and Not Lactate Uptake
Open accessAbstract
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.
Overview
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
Cites
Statistics
Verification
Claims the paper makes
25 Own interpretation · 22 Not checked yet · 21 Own result · 8 Own method · 2 No basis given
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Similar neuronal cytosolic NADH transients occur in vivo with normal sensory stimulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Similar neuronal cytosolic NADH transients occur in vivo with normal sensory stimulation
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Cytosolic NADH transients reflect increased neuronal glycolysis upon stimulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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)”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Stimulation produces transient increases of cytosolic NADH:NAD+ in individual neurons
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Transients in cytosolic NADH do not simply reflect mitochondrial NAD(P)H transients
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The increase in cytosolic NADH:NAD+ ratio (hereafter referred to as NADHCYT) was quite substantial, with 60 stimuli typically producing a change from a baseline ratio of ~1:1000 up to a stimulated ratio of ~1:500, a ~2-fold change (corresponding to a Peredox LT of 1.73 ± 0.01 ns at baseline and 1.88 ± 0.01 ns when stimulated; mean ± SEM, n=166 neurons).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Stimulation produces transient increases of cytosolic NADH:NAD+ in individual neurons
plaindirectn = 166- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the presence of the MCT inhibitor, the NADHCYT response to direct application of exogenous lactate was much smaller (27% ± 2% of the original response, mean ± SEM, n=36 neurons), as expected if lactate uptake is mostly blocked.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Lactate import does not contribute to neuronal NADHCYT transients
plaindirectn = 36- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Upon brief synaptic stimulation of the DGNs by electrical stimulation in the molecular layer of the dentate gyrus (60 brief pulses), there was a prominent and reliable elevation of the cytosolic NADH:NAD+ ratio for a period of about 3 minutes (Figure 1A–C).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Stimulation produces transient increases of cytosolic NADH:NAD+ in individual neurons
plaindirectn = 166- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Next we applied the MCT inhibitor AR-C155858 (2 μM), and observed a small decline in the resting NADHCYT”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Lactate import does not contribute to neuronal NADHCYT transients
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“With application of the MCT inhibitor, there was no significant change in these neuronal intracellular [lactate] transients (Fig. 3G)”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Lactate import does not contribute to neuronal NADHCYT transients
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 18
- Probably not a substantial claim. 15
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Astrocyte stimulation by glutamate is neither sufficient nor necessary for neuronal NADH transients
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Similar neuronal cytosolic NADH transients occur in vivo with normal sensory stimulation
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Similar neuronal cytosolic NADH transients occur in vivo with normal sensory stimulation
plaindirectn = 59- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Cytosolic NADH transients reflect increased neuronal glycolysis upon stimulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Lactate import does not contribute to neuronal NADHCYT transients
plaindirectn = 54- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The LDH inhibitor GSK-2837808A specifically inhibits lactate dehydrogenase.
- Also stated in: § Lactate import does not contribute to neuronal NADHCYT transients · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Cytosolic NADH transients reflect increased neuronal glycolysis upon stimulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > The NADH biosensor reports metabolic transients specifically in neuronal cytosol
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Cytosolic NADH transients reflect increased neuronal glycolysis upon stimulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > INTRODUCTION
What the sources say
- Not checked yetcites Clarke and Sokoloff, 1994
- Not checked yetcites Madsen et al., 1999 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Astrocyte-to-neuron lactate shuttling may occur at rest, but not during neuronal stimulation
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results support the possibility of an ANLS that functions at rest but not during neuronal stimulation.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Astrocyte-to-neuron lactate shuttling may occur at rest, but not during neuronal stimulation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Similar neuronal cytosolic NADH transients occur in vivo with normal sensory stimulation
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Lactate import does not contribute to neuronal NADHCYT transients
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“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.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Stimulation produces transient increases of cytosolic NADH:NAD+ in individual neurons
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Experimental Models and Subject Details
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Quantification and Statistical Analyses
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Method Details
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Method Details
What the sources say
- Not checked yetcites Andermann et al., 2010
- Not checked yetcites O’Connor et al., 2010
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Method Details
What the sources say
- Not checked yetcites Zhang et al., 2002
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For this reason, we mostly measured the net lifetime change for the transients, relative to baseline (ΔLT).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Quantification and Statistical Analyses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
What the sources say
- Not checked yetcites Crow and Kushmerick, 1982
- Not checked yetcites Spriet, 1989
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Method Details
What the sources say
- Not checked yetcites Halestrap and Denton, 1974
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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%.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Quantification and Statistical Analyses
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“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)”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
What the sources say
- Not checked yetcites Dienel, 2012 source
- Not checked yetcites Glenn et al., 2015
- Not checked yetcites Collins et al., 1970
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Likewise, green glucose sensor fluorescence produced a bleedthrough of ~5.9% to the red channel.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Quantification and Statistical Analyses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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”
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“With brief neuronal excitation in an acute hippocampal slice, NADHCYT rises rapidly and remains elevated for ∼2–3 min, reflecting a temporary imbalance favoring production of NADH over its recycling back to NAD+.”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Díaz-García et al., 2017
In the citing paper
“The NADHCYT transients decrease with inhibition of glycolysis but not of the MAS, indicating that increased neuronal glycolysis upon stimulation is the main cause of the NADHCYT transients.”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Díaz-García et al., 2017
In the citing paper
“Pharmacologic blockade of MCT or of LDH abolishes the elevation of NADHCYT in response to exogenous lactate but not in response to stimulation, which rules out a role of lactate import in producing the transient increases in neuronal NADHCYT.”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Díaz-García et al., 2017
In the citing paper
“In dentate granule neurons, MCT inhibition led to higher peaks of NADHCYT as well as smaller dips in glucose, suggesting that the elevated NADHCYT also exerted back pressure on glycolysis, presumably on the GAPDH equilibrium (Díaz-García et al., 2017).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Díaz-García et al., 2017
Citations
Cites
Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation.
Kwong, K. K., Belliveau, J. W., Chesler, D. A., Goldberg, I. E., Weisskoff, R. M., Poncelet, B. P., Kennedy, D. N., Hoppel, B. E., Cohen, M. S., & Turner, R. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.12.5675 · Cited by 4,212 · cited 2×
“imaging experiments (Kwong et al., 1992): blood oxygenation level is somewhat paradoxically increased in activated regions, despite the increased metabolic demand.”
Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq
Zeisel, A., Muñoz-Manchado, A. B., Codeluppi, S., Lönnerberg, P., La Manno, G., Juréus, A., Marques, S., Munguba, H., He, L., Betsholtz, C., et al. (2015) · Science · doi:10.1126/science.aaa1934 · Cited by 3,124 · cited 1×
“…(Salway, 2004; in neurons, mainly the malate-aspartate shuttle [MAS], McKenna et al., 2006); unbiased proteomics and transcriptomics surveys of central neurons reveal that these are by far the dominant NADH dehydrogenase enzymes in the cytosol (Sharma et al., 2015; Zeisel et al., 2015; Figure S1).”
Pellerin, L., & Magistretti, P. J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.22.10625 · Cited by 2,927
Brain energy metabolism: focus on Astrocyte-neuron metabolic cooperation
Bélanger, M., Allaman, I., & Magistretti, P. J. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.016 · Cited by 2,313 · cited 2×
“…an ‘‘astrocyte-neuron lactate shuttle’’ (ANLS), which proposes that astrocytes are stimulated by neuronal glutamate release to convert more glucose to lactate, which is then Cell released by the astrocytes to serve as fuel for the neighboring neurons (Bélanger et al., 2011; Pellerin et al., 1998).”
Fox, P. T., & Raichle, M. E. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.4.1140 · Cited by 2,056 · cited 2×
“However, with brain activation, glucose consumption increases much more than oxygen consumption (Fox and Raichle, 1986; Fox et al., 1988).”
Williamson, D., Lund, P., & Krebs, H. (1967) · Biochemical Journal · doi:10.1042/bj1030514 · Cited by 1,871 · cited 2×
“This produced a large and prompt increase in NADHCYT, likely mediated by the rapid action of LDH, which converts NAD to NADH in parallel with the conversion of lactate to pyruvate (Williamson et al., 1967; Hung et al., 2011).”
Nonoxidative Glucose Consumption During Focal Physiologic Neural Activity
Fox, P. T., Raichle, M. E., Mintun, M. A., & Dence, C. (1988) · Science · doi:10.1126/science.3260686 · Cited by 1,796 · cited 2×
“However, with brain activation, glucose consumption increases much more than oxygen consumption (Fox and Raichle, 1986; Fox et al., 1988).”
ScanImage: Flexible software for operating laser scanning microscopes
Pologruto, T. A., Sabatini, B. L., & Svoboda, K. (2003) · BioMedical Engineering OnLine · doi:10.1186/1475-925x-2-13 · Cited by 1,300
Basic Neurochemistry???Molecular, Cellular, and Medical Aspects
Long, D. M. (2006) · Neurosurgery Quarterly · doi:10.1097/01.wnq.0000203279.82150.41 · Cited by 1,294
Sensitive red protein calcium indicators for imaging neural activity
Dana, H., Mohar, B., Sun, Y., Narayan, S., Gordus, A. G., Hasseman, J. P., Tsegaye, G., Holt, G. T., Hu, A., Walpita, D., et al. (2016) · eLife · doi:10.7554/elife.12727 · Cited by 1,052
Cited by
Sorted by citations
Lactate in the brain: from metabolic end-product to signalling molecule
Magistretti, P. J., & Allaman, I. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2018.19 · Cited by 1,298
Brain Glucose Metabolism: Integration of Energetics with Function
Dienel, G. A. (2018) · Physiological Reviews · doi:10.1152/physrev.00062.2017 · Cited by 911
Astrocyte-neuron metabolic cooperation shapes brain activity
Bonvento, G., & Bolaños, J. P. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.07.006 · Cited by 580
ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism
Qi, G., Mi, Y., Shi, X., Gu, H., Brinton, R. D., & Yin, F. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108572 · Cited by 379
Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism
Yellen, G. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201803152 · Cited by 371
“Fluorescent biosensor measurement of NADHCYT in neurons during excitation has helped to resolve the role of glycolysis and intercellular lactate transport in the acute metabolic response (Díaz-García et al., 2017).”
BackgroundSelf-citationGlutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration
Andersen, J. V., Markussen, K. H., Jakobsen, E., Schousboe, A., Waagepetersen, H. S., Rosenberg, P. A., & Aldana, B. I. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108719 · Cited by 392
“Although widely endorsed (Mächler et al., 2016; Suzuki et al., 2011), the dependence of neurons on astrocyte-derived lactate during periods of increased activity has been challenged and has proved difficult to demonstrate in vivo (Diaz-Garcia et al., 2017; Dienel, 2017).”
Protein lactylation induced by neural excitation
Hagihara, H., Shoji, H., Otabi, H., Toyoda, A., Katoh, K., Namihira, M., & Miyakawa, T. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109820 · Cited by 349
Immunometabolism in the Brain: How Metabolism Shapes Microglial Function
Bernier, L., York, E. M., & MacVicar, B. A. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.08.008 · Cited by 301
Energy matters: presynaptic metabolism and the maintenance of synaptic transmission
Li, S., & Sheng, Z. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00535-8 · Cited by 285
Energy metabolism in ALS: an underappreciated opportunity?
Vandoorne, T., Bock, K. D., & Bosch, L. V. D. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1835-x · Cited by 260
“Indeed, neurons also take up and metabolize glucose and increase glucose consumption in an activity-dependent manner [6, 47, 144].”
BackgroundPleiotropic Mitochondria: The Influence of Mitochondria on Neuronal Development and Disease
Rangaraju, V., Lewis, T. L., Hirabayashi, Y., Bergami, M., Motori, E., Cartoni, R., Kwon, S., & Courchet, J. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.1157-19.2019 · Cited by 264
“…circuits rely heavily on mitochondrial respiration, although other metabolic pathways contribute to neuronal bioenergetics as well, including neuronal glycolysis (Zala et al., 2013; Rangaraju et al., 2014; Pathak et al., 2015; Jang et al., 2016; Ashrafi et al., 2017; Díaz-García et al., 2017).”
BackgroundMyelin dynamics: protecting and shaping neuronal functions
Saab, A. S., & Nave, K. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.09.013 · Cited by 270
Alzheimer’s Disease: From Firing Instability to Homeostasis Network Collapse
Frère, S. G. A., & Slutsky, I. (2018) · Neuron · doi:10.1016/j.neuron.2017.11.028 · Cited by 242
Metabolic Dysregulation Contributes to the Progression of Alzheimer’s Disease
Yan, X., Hu, Y., Wang, B., Wang, S., & Zhang, X. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.530219 · Cited by 230
Hladky, S. B., & Barrand, M. A. (2018) · Fluids and Barriers of the CNS · doi:10.1186/s12987-018-0113-6 · Cited by 206
Glucose metabolic crosstalk and regulation in brain function and diseases
Zhang, S., Lachance, B. B., Mattson, M. P., & Jia, X. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102089 · Cited by 213
Jha, M. K., & Morrison, B. M. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.07.009 · Cited by 203
Mitochondrial heterogeneity and homeostasis through the lens of a neuron
Pekkurnaz, G., & Wang, X. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00594-w · Cited by 201
Rose, J., Brian, C., Pappa, A., Panayiotidis, M. I., & Franco, R. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.536682 · Cited by 196
Pathophysiological subtypes of Alzheimer’s disease based on cerebrospinal fluid proteomics
Tijms, B. M., Gobom, J., Reus, L. M., Jansen, I. E., Hong, S., Dobričić, V., Kilpert, F., ten Kate, M., Barkhof, F., Tsolaki, M., et al. (2020) · Brain · doi:10.1093/brain/awaa325 · Cited by 197
“Neurons can increase neuronal glycolysis during neuronal stimulation (Dı́az-Garcı́a et al., 2017).”
BackgroundMitochondria, Metabolism, and Redox Mechanisms in Psychiatric Disorders
Kim, Y., Vadodaria, K. C., Lenkei, Z., Kato, T., Gage, F. H., Marchetto, M. C., & Santos, R. (2018) · Antioxidants and Redox Signaling · doi:10.1089/ars.2018.7606 · Cited by 193
Lactate from astrocytes fuels learning-induced mRNA translation in excitatory and inhibitory neurons
Descalzi, G., Gao, V., Steinman, M. Q., Suzuki, A., & Alberini, C. M. (2019) · Communications Biology · doi:10.1038/s42003-019-0495-2 · Cited by 188
Abrantes, H. D. C., Briquet, M., Schmuziger, C., Restivo, L., Puyal, J., Rosenberg, N., Rocher, A., Offermanns, S., & Chatton, J. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.2092-18.2019 · Cited by 185
Energy Metabolism Decline in the Aging Brain—Pathogenesis of Neurodegenerative Disorders
Błaszczyk, J. W. (2020) · Metabolites · doi:10.3390/metabo10110450 · Cited by 166
Barros, L. F., & Weber, B. (2018) · The Journal of Physiology · doi:10.1113/jp274944 · Cited by 154
“Stimulation of neuronal glycolysis by electrical activity was inferred from a rise in neuronal NADH/NAD+ that was insensitive to MCT2 blockage, which was interpreted as evidence against ANLS (Diaz-Garcia et al. 2017).”
BackgroundInfluentialmTOR/AMPK signaling in the brain: Cell metabolism, proteostasis and survival
Garza-Lombó, C., Schroder, A. L., Reyes‐Reyes, E. M., & Franco, R. (2018) · Current Opinion in Toxicology · doi:10.1016/j.cotox.2018.05.002 · Cited by 169
Glial Connexins and Pannexins in the Healthy and Diseased Brain
Giaume, C., Naus, C. C., Sáez, J. C., & Leybaert, L. (2021) · Physiological Reviews · doi:10.1152/physrev.00043.2018 · Cited by 154
Glycerol-3-phosphate biosynthesis regenerates cytosolic NAD+ to alleviate mitochondrial disease
Liu, S., Fu, S., Wang, G., Cao, Y., Li, L., Li, X., Yang, J. J., Li, N., Shan, Y., Cao, Y., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.06.013 · Cited by 159
Brain energy metabolism: Astrocytes in neurodegenerative diseases.
Chen, Z., Yuan, Z., Yang, S., Zhu, Y., Xue, M., Zhang, J., & Leng, L. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13982 · Cited by 153
Wei, Y., Miao, Q., Zhang, Q., Mao, S., Li, M., Xu, X., Xia, X., Wei, K., Fan, Y., Zheng, X., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01476-4 · Cited by 153
Wu, A., Lee, D., & Xiong, W. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713398 · Cited by 164
Andersen, J. V., & Schousboe, A. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15811 · Cited by 161
Myeloid Cells in Glioblastoma Microenvironment
Leo, A. D., Ugolini, A., & Veglia, F. (2020) · Cells · doi:10.3390/cells10010018 · Cited by 150
The role of astrocyte structural plasticity in regulating neural circuit function and behavior
Lawal, O., Ulloa Severino, F. P., & Eroglu, C. (2022) · Glia · doi:10.1002/glia.24191 · Cited by 142
“This energy source could be significant in meet- ing the metabolic demands of neurons during wake (de Tredern et al., 2021; Díaz-García et al., 2017).”
BackgroundJurcău, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111847 · Cited by 151
Synapses: The Brain’s Energy-Demanding Sites
Faria‐Pereira, A., & Morais, V. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073627 · Cited by 152
Neurons require glucose uptake and glycolysis in vivo
Li, H., Guglielmetti, C., Sei, Y. J., Zilberter, M. Y., Page, L. M. L., Shields, L. Y., Yang, J. L., Nguyen, K., Tiret, B., Gao, X. Z., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112335 · Cited by 143
Yao, S., Xu, M.-D., Wang, Y., Zhao, S., Wang, J., Chen, G.-F., Chen, W., Liu, J., Huang, G., Sun, W.-J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36209-5 · Cited by 144
Astrocyte metabolism and signaling pathways in the CNS
Zhang, Y.-M., Qi, Y., Gao, Y.-N., Chen, W.-G., Zhou, T., Zang, Y., & Li, J. X. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1217451 · Cited by 152
AMPK-Regulated Astrocytic Lactate Shuttle Plays a Non-Cell-Autonomous Role in Neuronal Survival
Muraleedharan, R., Gawali, M. V., Tiwari, D., Sukumaran, A., Oatman, N., Anderson, J., Nardini, D., Bhuiyan, M. A. N., Tkáč, I., Ward, A. L., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108092 · Cited by 134
Arousal-induced cortical activity triggers lactate release from astrocytes
Zuend, M., Saab, A. S., Wyss, M. T., Ferrari, K. D., Hösli, L., Looser, Z. J., Stobart, J. L., Durán, J., Guinovart, J. J., Barros, L. F., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0170-4 · Cited by 128
Non-Canonical Control of Neuronal Energy Status by the Na+ Pump
Baeza-Lehnert, F., Saab, A. S., Gutiérrez, R., Larenas, V., Díaz, E., Horn, M., Vargas, M., Hösli, L., Stobart, J., Hirrlinger, J., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.11.005 · Cited by 126
Brown adipocyte glucose metabolism: a heated subject
Hankir, M. K., & Klingenspor, M. (2018) · EMBO Reports · doi:10.15252/embr.201846404 · Cited by 130
“What ensued was a heated and lengthy debate about precisely how and where glucose is handled by brain cells to power neuronal activity, with glycolytic and oxidative processes at presynaptic and postsynaptic sites as well as in astrocytes being tabled [2 – 5].”
Heterogeneity of Astrocytes in Grey and White Matter
Köhler, S., Winkler, U., & Hirrlinger, J. (2021) · Neurochemical Research · doi:10.1007/s11064-019-02926-x · Cited by 123
Han, R., Liang, J., & Zhou, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115887 · Cited by 125
Lipid metabolism in astrocytic structure and function
Lee, J. A., Hall, B., Allsop, J., Alqarni, R., & Allen, S. P. (2021) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2020.07.017 · Cited by 116
A turquoise fluorescence lifetime-based biosensor for quantitative imaging of intracellular calcium
van der Linden, F. H., Mahlandt, E. K., Arts, J. J. G., Beumer, J., Puschhof, J., de Man, S. M. A., Chertkova, A. O., Ponsioen, B., Clevers, H. C., van Buul, J. D., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-27249-w · Cited by 117
Adaptive responses to neurodegenerative stress in glaucoma
Calkins, D. J. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.100953 · Cited by 118
García-Rodríguez, D., & Giménez-Cassina, A. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.732120 · Cited by 129
Neurons rely on glucose rather than astrocytic lactate during stimulation
Díaz‐García, C. M., & Yellen, G. (2018) · Journal of Neuroscience Research · doi:10.1002/jnr.24374 · Cited by 107
Self-citationPowerhouse of the mind: mitochondrial plasticity at the synapse
Rossi, M., & Pekkurnaz, G. (2019) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.02.001 · Cited by 109
Mechanisms for the maintenance and regulation of axonal energy supply
Chamberlain, K. A., & Sheng, Z. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24411 · Cited by 111
Koveal, D., Rosen, P. C., Meyer, D. J., Díaz‐García, C. M., Wang, Y., Cai, L., Chou, P. J., Weitz, D. A., & Yellen, G. (2022) · Nature Communications · doi:10.1038/s41467-022-30685-x · Cited by 107
Self-citationGSEA of mouse and human mitochondriomes reveals fatty acid oxidation in astrocytes
Eraso‐Pichot, A., Brasó‐Vives, M., Golbano, A., Menacho, C., Claro, E., Galea, E., & Masgrau, R. (2018) · Glia · doi:10.1002/glia.23330 · Cited by 105
“Results in favor of or against the hypothesis have been reported from animal studies in vivo (Ashrafi & Ryan, 2017; Diaz-Garcia et al., 2017; Mächler et al., 2016), and illustrate the complexity of brain metabolism.”
ResultMoutaux, E., Charlot, B., Genoux, A., Saudou, F., & Cazorla, M. (2018) · Lab on a Chip · doi:10.1039/c8lc00694f · Cited by 102
Lactate is an energy substrate for rodent cortical neurons and enhances their firing activity
Karagiannis, A., Gallopin, T., Lacroix, A., Plaisier, F., Piquet, J., Geoffroy, H., Hepp, R., Naudé, J., Gac, B. L., Egger, R., et al. (2021) · eLife · doi:10.7554/elife.71424 · Cited by 108
“This lactate 459 sensitivity is consistent with lactate transport and oxidization in hypothalamic and 460 cortical neurons (Ainscow et al., 2002;Sada et al., 2015;Diaz-Garcia et al., 2017) 461 which are low in beta cells (Sekine et al., 1994;Pullen et al., 2011).”
BackgroundA general method for the development of multicolor biosensors with large dynamic ranges
Hellweg, L., Edenhofer, A., Barck, L., Huppertz, M.-C., Frei, M. S., Tarnawski, M., Bergner, A., Koch, B., Johnsson, K., & Hiblot, J. (2023) · Nature Chemical Biology · doi:10.1038/s41589-023-01350-1 · Cited by 108
Brain energy metabolism: A roadmap for future research
Rae, C. D., Baur, J. A., Borges, K., Dienel, G. A., Díaz‐García, C. M., Douglass, S. R., Drew, K. L., Duarte, J. M. N., Durán, J., Kann, O., et al. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16032 · Cited by 113
Self-citationDíaz‐García, C. M., Lahmann, C., Martínez‐François, J. R., Li, B., Koveal, D., Nathwani, N., Rahman, M., Keller, J. P., Marvin, J. S., Looger, L. L., et al. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24433 · Cited by 99
Self-citationDíaz‐García, C. M., Meyer, D. J., Nathwani, N., Rahman, M., Martínez‐François, J. R., & Yellen, G. (2021) · eLife · doi:10.7554/elife.64821 · Cited by 98
Self-citationEmerging roles of brain metabolism in cognitive impairment and neuropsychiatric disorders
Morella, I., Brambilla, R., & Morè, L. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104892 · Cited by 96
Bak, L. K., & Walls, A. B. (2018) · The Journal of Physiology · doi:10.1113/jp274945 · Cited by 93
“Further, Lundgaard et al. (2015) and Diaz-Garcia et al. (2017), employing a near-infrared 2-deoxyglucose probe and redox biosensors, respectively, showed that glucose is metabolised by neurons in an activity-dependent manner in situ in awake mice.”
Skotte, N. H., Andersen, J. V., Santos, A., Aldana, B. I., Willert, C. W., Nørremølle, A., Waagepetersen, H. S., & Nielsen, M. L. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.052 · Cited by 92
“extent in neurons compared with glial cells and, therefore, primarily reflect neuronal metabolism (Bak et al., 2006a; Achanta et al., 2017; Dı́az-Garcı́a et al., 2017).”
BackgroundAxonal energy metabolism, and the effects in aging and neurodegenerative diseases
Yang, S., Park, J. H., & Lu, H.-C. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00634-3 · Cited by 94
Mitochondria in Neuronal Health: From Energy Metabolism to Parkinson's Disease
Mahadevan, H. M., Hashemiaghdam, A., Ashrafi, G., & Harbauer, A. B. (2021) · Advanced Biology · doi:10.1002/adbi.202100663 · Cited by 112
Lactate topography of the human brain using hyperpolarized 13C-MRI
Lee, C. Y., Soliman, H., Geraghty, B. J., Chen, A. P., Connelly, K. A., Endre, R., Perks, W. J., Heyn, C., Black, S. E., & Cunningham, C. H. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.116202 · Cited by 88
Groten, C. J., & MacVicar, B. A. (2022) · Communications Biology · doi:10.1038/s42003-022-03848-1 · Cited by 93
Neuroprotection by glucose‐6‐phosphate dehydrogenase and the pentose phosphate pathway
Tang, B. L. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.29004 · Cited by 85
Visser, P. J., Reus, L. M., Gobom, J., Jansen, I. E., Dicks, E., van der Lee, S. J., Tsolaki, M., Verhey, F. R. J., Popp, J., Martínez‐Lage, P., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00521-3 · Cited by 92
Recent insights on astrocyte mechanisms in CNS homeostasis, pathology, and repair
Hart, C. G., & Karimi‐Abdolrezaee, S. (2021) · Journal of Neuroscience Research · doi:10.1002/jnr.24922 · Cited by 88
Consequences of Metabolic Disruption in Alzheimer's Disease Pathology
Ryu, J. C., Zimmer, E. R., Rosa‐Neto, P., & Yoon, S. O. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00755-y · Cited by 87
Lactate Transporters Mediate Glia-Neuron Metabolic Crosstalk in Homeostasis and Disease
Jha, M. K., & Morrison, B. M. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.589582 · Cited by 81
Lactate and Lactylation in the Brain: Current Progress and Perspectives
Li, R., Yang, Y., Wang, H., Zhang, T., Duan, F., Wu, K., Yang, S., Xu, K., Jiang, X., & Sun, X. (2023) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-023-01335-7 · Cited by 82
Ligneul, C., Palombo, M., Hernández-Garzón, E., Carrillo-de Sauvage, M.-A., Flament, J., Hantraye, P., Brouillet, E., Bonvento, G., Escartin, C., & Valette, J. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.02.046 · Cited by 77
York, E. M., Zhang, J., Choi, H. B., & MacVicar, B. A. (2020) · Glia · doi:10.1002/glia.23913 · Cited by 81
“Local synaptic activity itself poses a dynamic metabolic challenge within the brain, met by tightly regulated supplies of glucose, oxygen, and alternative fuels (Diaz-Garcia et al., 2017; Iadecola, 2017; Murphy-Royal et al., 2020).”
BackgroundGlial glucose fuels the neuronal pentose phosphate pathway for long-term memory
de Tredern, É., Rabah, Y., Pasquer, L., Minatchy, J., Plaçais, P.-Y., & Préat, T. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109620 · Cited by 79
Fluorescent Biosensors for Neuronal Metabolism and the Challenges of Quantitation
Koveal, D., Díaz‐García, C. M., & Yellen, G. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2020.02.011 · Cited by 77
Self-citationAerobic Glycolysis in the Brain: Warburg and Crabtree Contra Pasteur
Barros, L. F., Ruminot, I., Martín, A. S., Lerchundi, R., Fernández‐Moncada, I., & Baeza‐Lehnert, F. (2020) · Neurochemical Research · doi:10.1007/s11064-020-02964-w · Cited by 77
Glycolysis-derived alanine from glia fuels neuronal mitochondria for memory in Drosophila
Rabah, Y., Francés, R., Minatchy, J., Guédon, L., Desnous, C., Plaçais, P.-Y., & Préat, T. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00910-y · Cited by 76
“In support of this opposing model, it was reported that neuronal glycolysis is upregulated for energy production in response to neuronal stimulation 13 .”
BackgroundMcConnell, H., Li, Z., Woltjer, R. L., & Mishra, A. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.04.005 · Cited by 74
“, 2016), although this is debated (DiNuzzo et al., 2010; Diaz-Garcia et al., 2017; Dienel, 2017).”
Wang, Y., Li, P., Xu, Y., Feng, L., Fang, Y., Song, G., Li, X., Zhu, Z., Wang, W., Mei, Q., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03303-4 · Cited by 77
“Instead, they propose ANLS functions at resting states but not under stimulation [51].”
Ruminot, I., Schmälzle, J., Leyton, B., Barros, L. F., & Deitmer, J. W. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17737012 · Cited by 73
Regional differences in brain glucose metabolism determined by imaging mass spectrometry
Kleinridders, A., Ferris, H. A., Reyzer, M. L., Rath, M., Soto, M., Manier, M. L., Spraggins, J. M., Yang, Z., Stanton, R. C., Caprioli, R. M., et al. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.03.013 · Cited by 70
“Precise control of neuronal glucose metabolism via the glycolytic and PPP is important for neuronal function, activation, and neuronal survival [27,28].”
BackgroundPamies, D., Sartori, C., Schvartz, D., González‐Ruiz, V., Pellerin, L., Nunes, C., Tavel, D., Maillard, V., Boccard, J., Rudaz, S. L., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084065 · Cited by 72
Lactate Attenuates Synaptic Transmission and Affects Brain Rhythms Featuring High Energy Expenditure
Hollnagel, J., Cesetti, T., Schneider, J., Vazetdinova, A., Valiullina, F., Lewen, A., Rozov, A. V., & Kann, O. (2020) · iScience · doi:10.1016/j.isci.2020.101316 · Cited by 66
Mitochondrial regulation of local supply of energy in neurons
López‐Doménech, G., & Kittler, J. T. (2023) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2023.102747 · Cited by 78
Long, D. M., Frame, A. K., Reardon, P. N., Cumming, R. C., Hendrix, D. A., Kretzschmar, D., & Giebultowicz, J. M. (2020) · Aging · doi:10.18632/aging.103373 · Cited by 67
Metabolic Control of Epilepsy: A Promising Therapeutic Target for Epilepsy
Fei, Y., Shi, R., Song, Z. Q., & Wu, J. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.592514 · Cited by 68
“Conversely, to support increased synaptic vesicle circulation, the glycolysis levels in activated neurons were significantly increased (2-fold change from baseline), especially in the pre-synaptic terminals (23).”
BackgroundDienel, G. A. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24387 · Cited by 65
“Neuronal glycolysis, not utilization of extracellular lactate (derived from astrocytic glucose or glycogen), is upregulated during stimulation of hippocampal slices in vitro and whisker barrel cortex in vivo (Diaz‐Garcia et al., 2017; Yellen, 2018).”
BackgroundNakamura, T., & Lipton, S. A. (2019) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.7916 · Cited by 67
“Additionally, neuronal stimulation in adult brains can temporarily trigger neuronal glycolysis (28).”
BackgroundRahman, M. H., Bhusal, A., Kim, J., Jha, M. K., Song, G. J., Go, Y., Jang, I., Lee, I., & Suk, K. (2020) · Nature Communications · doi:10.1038/s41467-020-19576-1 · Cited by 66
Lactate Supply Overtakes Glucose When Neural Computational and Cognitive Loads Scale Up
Dembitskaya, Y., Piette, C., Siaume‐Perez, S., Berry, H., Magistretti, P. J., & Venance, L. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2212004119 · Cited by 70
In Vivo Imaging with Genetically Encoded Redox Biosensors
Kostyuk, A. I., Panova, A. S., Kokova, A. D., Kotova, D. A., Maltsev, D. I., Podgorny, O. V., Belousov, V. V., & Bilan, D. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218164 · Cited by 66
Aerobic Glycolysis Is Required for Spatial Memory Acquisition But Not Memory Retrieval in Mice
Harris, R. A., Lone, A., Lim, H., Martínez, F. M., Frame, A. K., Scholl, T. J., & Cumming, R. C. (2019) · eNeuro · doi:10.1523/eneuro.0389-18.2019 · Cited by 60
“A separate study, using metabolic biosensors in hippocampal slices and brains of awake mice, revealed that neuronal stimulation is dependent on increased glucose consumption directly by neurons, not astrocytic-derived lactate (Díaz-García et al., 2017).”
BackgroundSynaptic energy metabolism and neuronal excitability, in sickness and health
Oyarzábal, A., & Marin‐Valencia, I. (2019) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12071 · Cited by 63
“Using in vivo and in vitro approaches, it was shown that glutamate or K released from presynaptic terminals during electrical stimulation failed to increase cytosolic NADH fluorescence transients in hippocampal neurons.(9) In contrast, most of the NADH detected in the cytoplasm resulted from increased neuronal glycoly…”
BackgroundCytoskeletal regulation guides neuronal trafficking to effectively supply the synapse
Aiken, J., & Holzbaur, E. L. F. (2021) · Current Biology · doi:10.1016/j.cub.2021.02.024 · Cited by 61
Weak neuronal glycolysis sustains cognition and organismal fitness
Jiménez-Blasco, D., Agulla, J., Lapresa, R., Macia, M. G., Bobo-Jiménez, V., García-Rodríguez, D., Manjarrés-Raza, I., Fernández, E., Jeanson, Y., Khoury, S., et al. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01049-0 · Cited by 65
“Naturally, neuronal glycolysis is amenable to transient activation during glutamatergic neurotransmission 25,37,38 or hypoxia 39 , where this pathway has energetic functions in specific subcellular compartments 40–43 .”
Shen, Y., Nasu, Y., Shkolnikov, I., Kim, A., & Campbell, R. E. (2020) · Neuroscience Research · doi:10.1016/j.neures.2020.01.011 · Cited by 59
Differentiation but not ALS mutations in FUS rewires motor neuron metabolism
Vandoorne, T., Veys, K., Guo, W., Sicart, A., Vints, K., Swijsen, A., Moisse, M., Eelen, G., Gounko, N. V., Fumagalli, L., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12099-4 · Cited by 59
Rothman, D. L., Dienel, G. A., Behar, K. L., Hyder, F., DiNuzzo, M., Giove, F., & Mangia, S. (2022) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x211064399 · Cited by 58
Metadata
- Authors
- Díaz-García, C. M., Mongeon, R., Lahmann, C., Koveal, D., Zucker, H., & Yellen, G.
- Affiliations
- Harvard University (US)
- Corresponding author
- Yellen, Gary
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 26
- Issue
- 2
- Pages
- 361-374.e4
- ISSN
- 1550-4131 (ISSN-L)
- 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
- FWCI
- 19.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
