The DOI matches its Crossref record; 331 of the 331 references it cites were found in a registry or an index; none of the 343 sources its claims cite is checked for support yet.
The energetic brain—A review from students to students
Open accessAbstract
The past 20 years have resulted in unprecedented progress in understanding brain energy metabolism and its role in health and disease. In this review, which was initiated at the 14th International Society for Neurochemistry Advanced School, we address the basic concepts of brain energy metabolism and approach the question of why the brain has high energy expenditure. Our review illustrates that the vertebrate brain has a high need for energy because of the high number of neurons and the need to maintain a delicate interplay between energy metabolism, neurotransmission, and plasticity. Disturbances to the energetic balance, to mitochondria quality control or to glia–neuron metabolic interaction may lead to brain circuit malfunction or even severe disorders of the CNS . We cover neuronal energy consumption in neural transmission and basic (‘housekeeping’) cellular processes. Additionally, we describe the most common (glucose) and alternative sources of energy namely glutamate, lactate, ketone bodies, and medium chain fatty acids. We discuss the multifaceted role of non‐neuronal cells in the transport of energy substrates from circulation (pericytes and astrocytes) and in the supply (astrocytes and microglia) and usage of different energy fuels. Finally, we address pathological consequences of disrupted energy homeostasis in the CNS . image
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Written from the paper’s full text.
TL;DR
This narrative review, initiated at the 14th International Society for Neurochemistry Advanced School, synthesizes the basic concepts of brain energy metabolism and explains why the brain has high energy expenditure. It covers neuronal ATP-consuming processes, alternative energy substrates, the role of non-neuronal cells, and how disturbed energy homeostasis contributes to CNS disorders and aging.
Key findings
- The human brain accounts for 20% of oxygen consumption and 25% of glucose utilization while representing only 2% of body weight (Sokoloff et al. 1977); most adult non-primate vertebrates use 2–8% of total basal metabolism for the CNS (Mink et al. 1981). Herculano-Houzel's analysis concluded that the whole-brain energy budget per neuron is fixed across species, so total glucose use is a linear function of neuron number.
- After a single action potential, rodent cortical neurons require ~4–8 × 10⁸ ATP molecules to restore Na⁺/K⁺ gradients via the Na⁺/K⁺-ATPase, making AP signaling the second largest metabolic cost after synaptic transmission. Estimates of the AP:postsynaptic-current energy ratio vary from 58:42% (Attwell and Laughlin 2001) to 20:80% (Alle et al. 2009).
- At a physiological spiking rate of 4 Hz, 15% of total gray-matter ATP maintains resting potential (Attwell and Laughlin 2001); Lennie (2003) attributed 13% of human neocortex energy to spiking, 28% to neuronal resting potential, 10% to glial resting potential, and the remainder to housekeeping. Housekeeping accounts for 25% of gray-matter energy and ~63%/~56% in partially/fully myelinated white matter (Harris and Attwell 2012).
- Engl et al. (2017) measured O₂ consumption in resting hippocampal slices: it fell 25% after actin cycling blockade, 22% after microtubule turnover blockade, and 18% after lipid and protein metabolism blockade, while blocking protein metabolism alone did not significantly change O₂ consumption.
Methods
- Narrative review (no primary data collection) initiated at the 14th ISN Advanced School (Varennes Jarcy, France, August 2017), synthesizing published literature on brain energy metabolism.
- Covers neuronal ATP consumption (presynaptic terminals, postsynaptic terminals, synaptic plasticity, AP generation/propagation, resting potential, housekeeping processes), energy sources (glucose, glutamate, lactate/ANLS, ketone bodies, medium-chain triglycerides), non-neuronal cells (pericytes, astrocytes, oligodendrocytes, microglia), and disease states (aging, T2DM, Alzheimer's, Parkinson's, ALS, MS, TBI/stroke).
- No systematic search strategy, inclusion criteria, or meta-analysis is described.
Limitations
- The authors state that brain energetics "can hardly be covered in a single review with satisfying depth" and apologize to scientists not cited "due to space limitations."
- The text makes evident that several key debates remain unresolved: the ANLS hypothesis is described as "critically viewed and challenged" with contradictory results across experimental settings and "the lack of a consensus-based method for real-time monitoring of metabolic dynamics at cellular resolution"; the proton leak mechanism "remains under debate"; and TBI glucose-transport data are "highly variable requiring further studies."
- The text notes that the estimated relative contributions of AP generation versus postsynaptic currents to energy expenditure "varied in the literature," and that the estimated cost of axonal transport does not account for tug-of-war events or dynein retrograde transport, so "further modeling is needed."
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Claims the paper makes
227 Not checked yet · 37 No basis given · 27 Own interpretation
In the paper
“in the absence of glucose, extracellular glutamate was metabolized and mostly converted into aspartate in rat brain homogenate (Haslam and Krebs, 1963).”
What the sources say
- Not checked yetcites Haslam and Krebs, 1963
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In the paper
“In vitro experiments in primary cultured neurons indicate that 10 mM of extracellular glutamate causes profound neuronal cell death under normoglycemic and normoxic conditions (Murphy et al. 1990;Khanna et al. 2003).”
What the sources say
- Not checked yetcites Murphy et al. 1990
- Not checked yetcites Khanna et al. 2003
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In the paper
“Studies based on substrate competition indicated that oxidation of glutamate in astrocytes as a source of energy is preferred compared to glucose and other substrates (Fig. 2), which suggests the robustness of glutamate use as a substrate for energy in these cells (McKenna et al. 2012).”
What the sources say
- Not checked yetcites McKenna et al. 2012
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In the paper
“However, when glucose is removed from media, extracellular glutamate (10 mM) no longer induces cell death (Rink et al. 2011).”
What the sources say
- Not checked yetcites Rink et al. 2011
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In the paper
“Induced alteration in metabolic substrate concentration, through voluntary exercise, has been shown to enhance metabolic enzymes involved in glycolysis, ATP synthesis, ATP transduction, and glutamate turnover (Ding et al. 2006).”
What the sources say
- Not checked yetcites Ding et al. 2006
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In the paper
“While performing extensive physical exercise, the cerebral metabolic ratio for carbohydrates, defined as cerebral molar uptake of (O 2 /(glucose + 1/2 lactate)), decreases from a resting value of 6 to < 2 (Smith et al. 2003;Quistorff et al. 2008).”
What the sources say
- Not checked yetcites Smith et al. 2003
- Not checked yetcites Quistorff et al. 2008
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In the paper
“In non-diabetic subjects, a 3-day fast increases the concentration of b-OHB from an average of 0.03-3.15mM in plasma, and from 0.05 to 0.98 mM in the brain (Pan et al. 2000).”
What the sources say
- Not checked yetcites Pan et al. 2000
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In the paper
“Furthermore, astrocytes and pericytes express comparable amounts of GLUT1 and GLUT4 (Castro et al. 2018).”
What the sources say
- Not checked yetcites Castro et al. 2018
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In the paper
“Triheptanoin was shown to partially replenish TCA cycle intermediates in epileptic mice (Hadera et al. 2014).”
What the sources say
- Not checked yetcites Hadera et al. 2014
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In the paper
“Additionally, numerous studies have demonstrated the beneficial effects of MCTGs as energy substrates in several neurological disorders such as epilepsy (Willis et al. 2010;Wla z et al. 2012;Chang et al. 2013;Tan et al. 2017), amyotrophic lateral sclerosis (Zhao et al. 2012;Tefera et al. 2016), stroke (Schwarzkopf et al. 2015), and cognitive impairments (Wang and Mitchell 2016).”
What the sources say
- Not checked yetcites Willis et al. 2010
- Not checked yetcites Wla z et al. 2012
- Not checked yetcites Chang et al. 2013
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In the paper
“Furthermore, a clinical study involving administration of sodium lactate reported a three-to fourfold increase in plasma lactate levels along with an average of 17% reduction in the rate of cerebral glucose uptake, indicative of a preferential cerebral uptake of lactate over glucose (Smith et al. 2003).”
What the sources say
- Not checked yetcites Smith et al. 2003
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In the paper
“Additionally, ketone bodies neither alter the plasma membrane potential of presynaptic terminals nor the pH of synaptic vesicles.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Rigorous physical activity increases lactate plasma levels from 0.6 mmol/L to around 2-3 mmol/ L, which then crosses the BBB via MCTs (Ide et al. 1999).”
What the sources say
- Not checked yetcites Ide et al. 1999
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In the paper
“Inhibition of the MAS and other transaminase reactions on the oxidation of energy substrates increases the oxidation of lactate and b-OHB in astrocytes, but has no significant effect on the rates of b-OHB oxidation and decreases the rate of lactate oxidation by synaptic terminals (McKenna et al. 1993).”
What the sources say
- Not checked yetcites McKenna et al. 1993
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In the paper
“b-OHB supports synaptic vesicle recycling, but reduces both endocytosis and, to a smaller extent, exocytosis (Hrynevich et al. 2016).”
What the sources say
- Not checked yetcites Hrynevich et al. 2016
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Preclinical studies report exercise training in mice augmented the expression of metabolically relevant genes (i.e., peroxisome proliferator-activated receptor gamma coactivator 1alpha, sirtuin-1, and citrate synthase) as well as increased mitochondrial DNA (mtDNA), suggestive of mitochondrial biogenesis in most brain regions studied (Steiner et al. 2011).”
What the sources say
- Not checked yetcites Steiner et al. 2011
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In the paper
“Decanoate facilitates glycolysis and lactate formation in astrocytes thereby providing fuel to neurons (Thevenet et al. 2016) and improving mitochondrial energy metabolism (Tan et al. 2017).”
What the sources say
- Not checked yetcites Thevenet et al. 2016
- Not checked yetcites Tan et al. 2017
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In the paper
“Octanoate was shown to promote ketogenesis in astrocytes (Thevenet et al. 2016) and to inhibit brain glycolysis in mice (McDonald et al. 2014) by reducing the maximal activity of the ratelimiting enzyme PFK (Tan et al. 2017).”
What the sources say
- Not checked yetcites Thevenet et al. 2016
- Not checked yetcites McDonald et al. 2014
- Not checked yetcites Tan et al. 2017
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, glucose intake of pericytes is four times higher than of endothelial cells, but similar to that of astrocytes, suggesting potential astrocyte/ pericyte complementary roles in maintaining glucose homeostasis in the brain.”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, vasoactive intestinal polypeptide as well as norepinephrine induce glycogenolysis in murine cortex (Magistretti et al. 1981).”
What the sources say
- Not checked yetcites Magistretti et al. 1981
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In the paper
“These outstanding social skills correlated with increased intelligence and are highlighted as necessary for more effective foraging and the exploitation of high-energy food; however, at the same time, the evolvement of these capabilities also imposes higher nutrient requirements (summarized in Dunbar & Shulz, 2017).”
What the sources say
- Not checked yetcites Dunbar & Shulz, 2017
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In the paper
“The human brain, however, accounts for 20% of oxygen (O 2 ) consumption and 25% of glucose utilization, although it amounts to only 2% of body weight (Sokoloff et al. 1977).”
What the sources say
- Not checked yetcites Sokoloff et al. 1977
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In the paper
“During humanization, multifaceted social behaviors evolved, such as formation of complex social groups, long-term parental investment, and cooperative foraging strategies.”
What the sources say
- Not checked yetcites Dunbar & Shulz, 2017
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In the paper
“According to Karbowski's estimates, which are based on the assumption of uniform scaling of neuronal density across species, cerebral energy per neuron increases with brain size (Karbowski 2009).”
What the sources say
- Not checked yetcites Karbowski 2009
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In the paper
“Disturbances to the energetic balance, to mitochondria quality control or to glia-neuron metabolic interaction may lead to brain circuit malfunction or even severe disorders of the CNS.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In light of the distal location of nerve terminals from cell bodies, synapses must rely on local ATP supplies, leaving them highly susceptible to mitochondriopathies.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, transmission failure was rescued at high stimulation frequencies by adding ATP exogenously and provided evidence that the reserve pool recruitment depends on ATPmit production downstream of PKA (protein kinase A) signaling.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The monitoring of ATPpresyn during AP firing in the absence of external Ca 2+ revealed that ATP utilized by the Na + /K + -ATPase alone represents a relatively small energy burden compared to downstream vesicle cycle processes at presynaptic terminals and that AP firing can persist even during phases of acute ATP synthesis blockade.”
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In the paper
“Plasticity of synapses can be mediated by changes in Ca 2+ concentration and/or the number of neurotransmitter receptors.”
plainconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“ATPpresyn levels are reduced by insufficiency of either glycolysis or mitochondrial function, indicating the requirement of activity-driven ATP synthesis to meet the energy demands of synaptic function.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Inhibition of glycolysis is accompanied by a reduction in endocytosis and a shift in remaining vesicular pH to more alkaline values.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, longterm potentiation (LTP), which can be triggered by activation of the postsynaptic NMDA receptors and insertion of more a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors into the postsynaptic membrane, enhances ATP supplement to potentiated synapses and energy consumption at postsynapses (Wieraszko 1982).”
What the sources say
- Not checked yetcites Wieraszko 1982
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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
“Therefore, ATPpresyn demand and activity-induced ATP synthesis should be synchronous and are essential for the maintenance of normal synaptic plasticity function.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The arrest of endocytosis at energy deficit conditions depends on the mechanochemical enzyme dynamin, which mediates membrane fission and depends cooperatively on synthesized guanosine triphosphate using ATP (Rangaraju et al. 2014).”
What the sources say
- Not checked yetcites Rangaraju et al. 2014
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In the paper
“Not only the generation of action potentials (AP), postsynaptic ion fluxes, presynaptic Ca 2+ entry, transmitter reuptake, and vesicle cycling but also the maintenance of the resting potential is a costly cellular neuronal function.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Completely blocking exocytosis does not significantly affect Ca 2+ influx during neuronal APs, suggesting that the synaptic vesicle cycle consumes most ATPpresyn.”
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In the paper
“highlighted by the positive correlation between the signaling-related energy usage predicted by Attwell and Laughlin (2001) and the distribution of mitochondria inside a cell, which was demonstrated to be higher in soma plus dendrites (62%) than in axon terminals (36%) (Wong-Riley 1989).”
What the sources say
- Not checked yetcites Wong-Riley 1989
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In the paper
“Moreover, activation of postsynaptic G protein-coupled receptors, such as metabotropic glutamate receptors (mGluR), triggers downstream events, which constrain ATP usage.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Additionally, mutations in Drosophila dynamin-related protein 1 (Drp1) depleted mitochondria from motor nerve terminals and interfered with mobilization of the reserve pool of synaptic vesicles and maintenance of neurotransmission (Verstreken et al. 2005).”
What the sources say
- Not checked yetcites Verstreken et al. 2005
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In the paper
“Inhibition of ATPmit production interfered with synaptic accumulation of mitochondria and subsequently abolished synaptic potentiation at the Drosophila neuromuscular junction (Tong 2007).”
What the sources say
- Not checked yetcites Tong 2007
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“direct experimental data in rat hippocampal nonmyelinated mossy fibers showed a minimal temporal overlap between the entry of Na + and the outflow of K + during an AP which results in one-third less energy necessary to elicit depolarization than in the Hodgkin-Huxley model, pointing to an AP : PSC ratio of 20 : 80% (Alle et al. 2009).”
What the sources say
- Not checked yetcites Alle et al. 2009
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Then, pyruvate can either enter the TCA cycle via pyruvate dehydrogenase and be metabolized via OxPhos in mitochondria to generate ATP or be converted to lactate or alanine by LDH or aminotransferase, respectively.”
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Furthermore, the muscle-type LDH5 having a greater V max is better equipped at converting pyruvate to lactate and supports higher glycolytic rates, but LDH1 exhibits a lower K m and is inhibited by low concentrations of pyruvate and by lactate.”
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In the paper
“Since lactate cannot diffuse passively across the BBB, it needs to be produced in situ within the brain and efficiently transported between cells (Fig. 2).”
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: unclear — It is unclear why the paper says 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
“In summary, higher expression of LDH5 suggests a higher rate of glycolysis in astrocytes and higher expression of LDH1 suggests lactate utilization as an energy source in neurons.”
hedgedcorrelational- 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
“This K + -mediated mechanism was suggested to be a general hallmark of neurometabolic coupling”
hedgedcorrelational- 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.
- Rests on an assumption: K+ is released at nodes of Ranvier during AP propagation, at serotonergic synapses, or at the cholinergic neuromuscular junction.
In the paper
“Lennie (2003) estimated that the spike-related energy expenditure is only 13% of total energy usage in human neocortex, attributing 28% and 10% to maintain the resting potential in neurons and glia, respectively, and the remaining to non-signaling ('housekeeping') processes (Lennie 2003).”
What the sources say
- Not checked yetcites Lennie 2003
hedged- 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.
In the paper
“while the classical Hodgkin-Huxley model for AP generation in the squid axon and a number of assumptions such as treating all neurons as identical (Attwell and Laughlin 2001) led to an assumed energy expenditure ratio for AP and PSC of 58 :”
What the sources say
- Not checked yetcites Attwell and Laughlin 2001
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
“While MCT2 and MCT4 are selectively expressed by neurons and astrocytes, respectively, MCT1 is expressed in astrocytes, oligodendrocytes, and endothelial cells of blood vessels (Debernardi et al. 2003;Pierre and Pellerin 2005;Rinholm et al. 2011).”
What the sources say
- Not checked yetcites Debernardi et al. 2003
- Not checked yetcites Pierre and Pellerin 2005
- Not checked yetcites Rinholm et al. 2011
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.
None of the sources cited for this claim have been checked yet.
In the paper
“It has been estimated that after one AP, rodent cortical neurons require between ~4-8 9 10 8 ATP molecules to restore the Na + and K + gradient through the Na + /K + -ATPase, suggesting the metabolic cost of AP signaling is the second largest after synaptic transmission (Lennie 2003;Hallermann et al. 2012).”
What the sources say
- Not checked yetcites Lennie 2003
- Not checked yetcites Hallermann et al. 2012
hedgeddirect- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Additionally, as lactate cannot be utilized directly, conversion of lactate to pyruvate, catalyzed by LDH, is essential as it then provides 18 ATPs via OxPhos (Pellerin and Magistretti 1994;Magistretti 2006).”
What the sources say
- Not checked yetcites Pellerin and Magistretti 1994
- Not checked yetcites Magistretti 2006
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
“This may increase by fasting or starvation to 5-6 mM (Owen et al. 1967), and to ~25 mM by dietary intervention or diabetic ketosis (Garber et al. 1974;Saudubray et al. 1981;Bonnefont et al. 1990;Mitchell et al. 1995).”
What the sources say
- Not checked yetcites Owen et al. 1967
- Not checked yetcites Garber et al. 1974
- Not checked yetcites Saudubray et al. 1981
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.
In the paper
“According to this, astrocytes serve as a 'lactate source' whereas neurons serve as a 'lactate sink' (Fig. 2).”
What the sources say
- Not checked yetcites Pellerin and Magistretti 1994
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 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
“In this context, when neuronal activity intensifies, astrocytes increase their glucose uptake, thus increasing the rate of glycolysis and lactate release into the extracellular space.”
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
“Additionally, mild elevation of blood ketone bodies occurs during the process of normal aging (Sengupta et al. 2010).”
What the sources say
- Not checked yetcites Sengupta 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.
In the paper
“when the activity of the MAS is limited (due to Ca 2+ -induced activation of the a-KG dehydrogenase, which competes with the malate/a-KG carrier for substrate), NAD + cannot be regenerated for glycolysis and NADH is not further oxidized in the electron transport chain (ETC), leading to an increase in cytosolic NADH concentration and a decrease in glycolysis and OxPhos.”
What the sources say
- Not checked yetcites Bak et al. 2009
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
“In opposition to the ANLS hypothesis, Bak and colleagues argue that oxidative metabolism of lactate within neurons only occurs during repolarization (and in the period between depolarizations) rather than during neurotransmission activity (Bak et al. 2009); and that neurons use lactate as an 'opportunistic' substrate when it is present (Bak and Walls 2018).”
What the sources say
- Not checked yetcites Bak et al. 2009
- Not checked yetcites Bak and Walls 2018
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. It may state two separate claims as one.
In the paper
“According to the model proposed by Bak et al., elevated neurotransmission may not increase oxidative metabolism of lactate; it decreases possibly because of a depolarization-induced increase in intracellular Ca 2+ concentration and a putative limitation of the MAS”
What the sources say
- Not checked yetcites Bak et al. 2009
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.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“However, due to unmet O 2 demand, plasma lactate levels are enhanced by conversion of pyruvate to lactate, which is an important step to regenerate NAD + , an essential substrate to carry out glycolysis and release ATP in the muscle (Lucas-Cuevas et al. 2015).”
What the sources say
- Not checked yetcites Lucas-Cuevas et al. 2015
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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Strenuous physical activity increases O 2 demand by the skeletal muscles leading to increased heart rate and respiration.”
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, the ANLS concept has been critically viewed and challenged due in part to contradictory results obtained in different experimental settings, and to the lack of a consensus-based method for real-time monitoring of metabolic dynamics at cellular resolution.”
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.
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 ANLS concept explains the role of lactate as an important energy source for brain function as well as defines the strong metabolic association between astrocytes and neurons.”
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. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“A sodium gradient drives this glutamate exchange, where one glutamate is co-transported with three Na + ions, thereby increasing the concentration of Na + within astrocytes.”
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: unclear — It is unclear why the paper says 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
“These results together with several converging lines of evidence suggest a critical role for alterations in global and regional brain metabolism in the pathogenesis of neurodegenerative diseases, indicating that physical activity could provide clinical benefit.”
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.
In the paper
“MCTGs are fatty acids with 7-12 carbon chain length; the most common MCTGs include heptanoate (C7), octanoate (C8), and decanoate (C10) (Sch€ onfeld and Wojtczak 2016).”
What the sources say
- Not checked yetcites Sch€ onfeld and Wojtczak 2016
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.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“It is suggested that most of the neurodegenerative diseases, as well as any other adverse changes in the brain, have notable changes in the ANLS and lead to imbalances in neurometabolic coupling (B elanger et al. 2011).”
What the sources say
- Not checked yetcites B elanger et al. 2011
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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“To further build upon these findings, for both research and diagnose purposes, positron emission tomography (PET) with the glucose analog F fluorodeoxyglucose (FDG) is commonly used as clinical diagnostic measure for local glucose metabolism.”
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“A higher Na + concentration within astrocytes leads to the activation of the a 2 subunit of the Na + /K + -ATPase which results in glycolysis stimulation (Mason 2017).”
What the sources say
- Not checked yetcites Mason 2017
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
“The concentration of b-OHB in plasma under healthy, fasted conditions is relatively low with reference values reported ~0.04 mM-0.08 mM (Hansen and Freier 1978).”
What the sources say
- Not checked yetcites Hansen and Freier 1978
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 states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Increased neuronal activity corresponds to an increased release of glutamate from presynaptic vesicles into the synapse.”
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“b-Hydroxybutyrate (b-OHB) is a metabolic intermediate that constitutes ~70% of ketone bodies produced in liver mitochondria mainly from the oxidation of fatty acids released from adipose tissue (Persson 1970).”
What the sources say
- Not checked yetcites Persson 1970
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.
It may state two separate claims as one.
In the paper
“Under normal physiological conditions, monocarboxylates cross the BBB with poor efficiency, but under starvation, the amount of ketones present in the blood and expression of MCTs in cells forming the BBB are increased (Hasselbalch et al. 1995).”
What the sources say
- Not checked yetcites Hasselbalch et al. 1995
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 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
“This stimulation leads to the production of lactate which is used as a substitute energy substrate by neurons.”
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
“For example, while some authors argue that neurons prefer lactate over glucose (Bouzier-Sore et al. 2003); others claim neurons are well equipped to metabolize glucose in an activity-dependent manner (Bak et al. 2009), which clearly opposes to the tight coupling of astrocytes to synaptic activity (Ruminot et al. 2017).”
What the sources say
- Not checked yetcites Bouzier-Sore et al. 2003
- Not checked yetcites Bak et al. 2009
- Not checked yetcites Ruminot et al. 2017
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. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Triheptanoin, a triglyceride of heptanoate, generates three molecules of heptanoate upon hydrolysis.”
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Pericytes are imperative for normal CNS functioning and have important roles in angiogenesis, vessel stabilization, endothelial cell regulation, and maintenance of the BBB (Fisher 2009;Hill et al. 2014).”
What the sources say
- Not checked yetcites Fisher 2009
- Not checked yetcites Hill et al. 2014
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Owing to their smaller size, MCTGs can readily diffuse into the brain as they do not require carnitine transporters unlike long chain fatty acids (Oldendorf 1973;Kuge et al. 1995).”
What the sources say
- Not checked yetcites Oldendorf 1973
- Not checked yetcites Kuge et al. 1995
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
“Heptanoate can directly enter into the brain or can be degraded into C5 ketones in the liver (Marin-Valencia et al. 2013).”
What the sources say
- Not checked yetcites Marin-Valencia et al. 2013
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
“They may also be found around the lymphatic capillaries in cases of developmental abnormalities (Petrova et al. 2004).”
What the sources say
- Not checked yetcites Petrova et al. 2004
hedgedcorrelational- 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
“Reports suggest that the pericyte-endothelial interaction regulates the basement membrane (Stratman et al. 2009(Stratman et al. , 2010) ) and the anatomical proximity between pericytes and endothelial cells indicates a probable role of pericytes in paracrine or juxtacrine signaling, as pericytes have been proposed to be involved in several signaling pathways including Angiopoietin-1, transforming”
What the sources say
- Not checked yetcites Stratman et al. 2009
- Not checked yetcites Stratman et al. 2010
- Not checked yetcites Gaengel et al. 2009
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.
In the paper
“The perivascular location and morphology of pericytes led to the suggestion that they may be contractile cells involved in regulation of capillary blood flow in response to vasoactive agents and neural activity (Sweeney et al. 2016).”
What the sources say
- Not checked yetcites Sweeney et al. 2016
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.
None of the sources cited for this claim have been checked yet.
In the paper
“C4 ketones and MCTGs can be further metabolized to acetyl-coenzyme A (CoA) and enter into the TCA cycle, primarily in astrocytes (Edmond et al. 1987;Marin-Valencia et al. 2013).”
What the sources say
- Not checked yetcites Edmond et al. 1987
- Not checked yetcites Marin-Valencia et al. 2013
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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The C5 ketones get converted into propionyl CoA, an anaplerotic molecule which can be carboxylated to succinyl coenzyme A (CoA) to feed the TCA cycle.”
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
“G6P can then be channeled into the glycolytic pathway to produce pyruvate, metabolized to glucose-1-phosphate for the synthesis of glycogen (Cataldo and Broadwell 1986;Dienel and Cruz 2015), or used in the PPP (Dringen et al. 2007).”
What the sources say
- Not checked yetcites Cataldo and Broadwell 1986
- Not checked yetcites Dienel and Cruz 2015
- Not checked yetcites Dringen et al. 2007
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.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“This neurometabolic coupling is a salient physiological characteristic of the brain function and has formed the basis for understanding neuroenergetics.”
boosteddirect- 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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. 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.
In the paper
“While the PPP is only a minor contributor to the total glucose oxidation, it generates NADPH, an important molecule for maintaining the antioxidant-reduced glutathione, as well as precursors for nucleotide synthesis (Dringen et al. 2007).”
What the sources say
- Not checked yetcites Dringen et al. 2007
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. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Astrocytes are the most abundant glial cells in the brain and display a number of active roles critical for CNS function (Nedergaard et al. 2003;Barros et al. 2018b), including regulation of neurotransmitters (Anderson and Swanson 2000), supplying substrates to neurons for OxPhos (Pellerin et al. 1998), maintaining water homeostasis (Simard and Nedergaard 2004;Salman et al. 2017a), and regulating”
What the sources say
- Not checked yetcites Nedergaard et al. 2003
- Not checked yetcites Barros et al. 2018b
- Not checked yetcites Anderson and Swanson 2000
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Astrocytes have extensive processes originating from the soma; some of these ensheath synapses (Ventura and Harris 1999) forming the 'tripartite synapse', while others known as 'endfeet' surround the brain arteries and capillaries (Araque et al. 1999;Oberheim et al. 2006;Barros et al. 2018b).”
What the sources say
- Not checked yetcites Ventura and Harris 1999
- Not checked yetcites Araque et al. 1999
- Not checked yetcites Oberheim et al. 2006
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 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
“This signal-induced regulation of glucose supply is thought to act in a complementary way; while vasoactive intestinal polypeptide acts locally within cortical columns, norepinephrine can control glycogen metabolism across adjacent columns.”
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.
In the paper
“In addition to glucose, astrocytes can efficiently use alternative energy substrates, such as mannose (Dringen et al. 1993); however, other carbohydrates like fructose or galactose are considered to be poor substrates in astrocytes (Dringen et al. 1993).”
What the sources say
- Not checked yetcites Dringen et al. 1993
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Astrocytic glycogenolysis is activated by extracellular increase in neurotransmitter concentrations as well as changes in the K + homeostasis following neuronal activity (Hof et al. 1988;Sickmann et al. 2009;Wang et al. 2012).”
What the sources say
- Not checked yetcites Hof et al. 1988
- Not checked yetcites Sickmann et al. 2009
- Not checked yetcites Wang et al. 2012
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.
It may state two separate claims as one.
In the paper
“Glycogen is predominantly found in astrocytes and seems to be connected to specific organelles and nonrandomly distributed (Cal ı et al. 2016).”
What the sources say
- Not checked yetcites Cal ı et al. 2016
hedgedcorrelational- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“The glycogen pool is dynamic and rapidly responds to changes in cerebral energetic demands by undergoing constant degradation and resynthesis (Swanson 1992), facilitated by glycogen synthase and glycogen phosphorylase expressed by astrocytes (Pellegri et al. 1996;Brown and Ransom 2007).”
What the sources say
- Not checked yetcites Swanson 1992
- Not checked yetcites Pellegri et al. 1996
- Not checked yetcites Brown and Ransom 2007
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Microglia can mount a molecular defense through the production of bioactive molecules that can be beneficial in some circumstances (i.e., phagocytosis of aberrant cells posing a threat to the CNS) and detrimental in others (i.e., when remaining primed in a disease state and being dysfunctional in response to a secondary injury, which can lead to loss of neural circuits) (Kettenmann et al. 2011;Dan”
What the sources say
- Not checked yetcites Kettenmann et al. 2011
- Not checked yetcites Daneman 2012
- Not checked yetcites Koss et al. 2019
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“While myelination is the primary function of oligodendrocytes, they also provide trophic support to neurons by secreting a wide variety of neurotrophins, including insulinlike growth factor-1, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor (Bradl and Lassmann 2010;Saab et al. 2013).”
What the sources say
- Not checked yetcites Bradl and Lassmann 2010
- Not checked yetcites Saab et al. 2013
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.
It may state two separate claims as one.
In the paper
“Microglia interact with neurons (i.e., scanning synapses) and thus contribute to the structure of neuronal networks and connectivity (Kettenmann et al. 2011).”
What the sources say
- Not checked yetcites Kettenmann et al. 2011
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.
It may state two separate claims as one.
In the paper
“Conversely, myelination is energetically costly and the metabolic costs of generating enough lipid and protein for myelin synthesis may be higher than the energy saved by accelerated axonal conduction (Nave and Werner 2014).”
What the sources say
- Not checked yetcites Nave and Werner 2014
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.
In the paper
“When activated, as indicated by a change in morphology toward an increased soma size and thicker proximal ramifications, microglia can migrate to the site of injury and proliferate (Bernhart et al. 2010).”
What the sources say
- Not checked yetcites Bernhart et al. 2010
plainconditional- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Therefore, the primary function of myelination is not to save energy, but rather to allow fast nerve conduction, thereby increasing information processing and improving cognitive power (Harris and Attwell 2012;Nave and Werner 2014).”
What the sources say
- Not checked yetcites Harris and Attwell 2012
- Not checked yetcites Nave and Werner 2014
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
“Microglia are cells of mesodermal origin that migrate into the CNS during embryonic development (Hickey and Kimura 1988).”
What the sources say
- Not checked yetcites Hickey and Kimura 1988
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. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Myelin acts as an electrical insulator by increasing the membrane resistance and decreasing membrane capacitance, resulting in increased conduction velocity while reducing axonal size requirements and neuronal metabolic demand.”
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Glucose is imperative for microglia survival and can enter microglia via transporters GLUT1, GLUT3, GLUT4, and GLUT5 (Payne et al. 1997;Wang et al. 2019).”
What the sources say
- Not checked yetcites Payne et al. 1997
- Not checked yetcites Wang et al. 2019
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.
It may state two separate claims as one.
In the paper
“G protein-coupled receptor 120 is known to bind unsaturated fatty acids and is possibly involved in their anti-inflammatory effects (Kalsbeek et al. 2016).”
What the sources say
- Not checked yetcites Kalsbeek et al. 2016
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. It may state two separate claims as one.
In the paper
“A recent study from Goyal et al. (2017) showed that agerelated decline in brain glucose uptake exceeds that of O 2 utilization, causing a loss of brain aerobic glycolysis.”
What the sources say
- Not checked yetcites Goyal et al. (2017)
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Conversely, GLUT5, exclusively expressed in microglial cells of the human and rat brain, is a very poor transporter of glucose and has been shown to facilitate the passage of fructose across the plasma membrane (Payne et al. 1997;Horikoshi et al. 2003).”
What the sources say
- Not checked yetcites Payne et al. 1997
- Not checked yetcites Horikoshi et al. 2003
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.
It may state two separate claims as one.
In the paper
“This inadequate glucose metabolism can arise from disruptions in supply, transport, or utilization, which likely all contribute to T2DM (Wardelmann et al. 2019).”
What the sources say
- Not checked yetcites Wardelmann et al. 2019
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.
In the paper
“Activation of microglia by ROS, especially nitric oxide (NO), modulates metabolic assembly based on glucose uptake and upregulates both anaerobic glycolysis and OxPhos of PPP.”
What the sources say
- Not checked yetcites Gimeno-Bay on et al. 2014
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These studies have identified increased adenosine monophosphate (AMP), ATP, purine, and pyrimidine levels (Ivanisevic et al. 2016) with the accumulation of these metabolites as hallmarks of multiple neurodegenerative diseases (Nyhan 2005;Yin et al. 2014).”
What the sources say
- Not checked yetcites Ivanisevic et al. 2016
- Not checked yetcites Nyhan 2005
- Not checked yetcites Yin et al. 2014
plaincorrelational- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Studies calculating brain glucose utilization over the course of human development, from birth to adulthood, have identified that energy metabolism peaks during early childhood (Kuzawa et al. 2014a) and declines during aging (Kuzawa et al. 2014a(Kuzawa et al. , 2014b;;Skoyles 2014).”
What the sources say
- Not checked yetcites Kuzawa et al. 2014a
- Not checked yetcites Kuzawa et al. 2014b
- Not checked yetcites Skoyles 2014
plaincorrelational- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Impeded cerebral glucose metabolism has been found in patients with T2DM; a condition commonly observed in Alzheimer patients (see below) (Mosconi et al. 2008;Baker et al. 2011).”
What the sources say
- Not checked yetcites Mosconi et al. 2008
- Not checked yetcites Baker et al. 2011
plaincorrelational- 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.
In the paper
“Tissue damage releases ATP which attracts microglia at the site of infection and consumes a vast amount of energy (Engl and Attwell 2015).”
What the sources say
- Not checked yetcites Engl and Attwell 2015
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“PPAR transcription factors have been shown to be widely distributed within the mammalian brain and to be involved in regulating the expression of genes involved in energy metabolism (Woods et al. 2003;Cimini et al. 2005;Cimini and Cer u 2008), making them strong candidates for possible key regulators of metabolic pathways impacted by brain aging.”
What the sources say
- Not checked yetcites Woods et al. 2003
- Not checked yetcites Cimini et al. 2005
- Not checked yetcites Cimini and Cer u 2008
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.
It may state two separate claims as one.
In the paper
“It was proposed that there are intrinsic neuronal features of generating and handling APs that render DA SNpc neurons more susceptible to mitochondrial dysfunction related to PD (Surmeier et al. 2012).”
What the sources say
- Not checked yetcites Surmeier et al. 2012
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.
None of the sources cited for this claim have been checked yet.
In the paper
“It has been suggested that T2DM accelerates AD development through perturbations in brain energy metabolism, advanced glycation end product and ROS production, and synaptic degeneration (Correia et al. 2012;Duarte 2015).”
What the sources say
- Not checked yetcites Correia et al. 2012
- Not checked yetcites Duarte 2015
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.
In the paper
“It has been demonstrated that protein levels of Drp1 are increased in AD and potentiate cell death (Park et al. 2014).”
What the sources say
- Not checked yetcites Park et al. 2014
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Therefore, reduction of mitochondrial fission leads to increased occurrences of mitochondrial fusion and results in neuroprotective effects in AD models (Itoh et al. 2013;Park et al. 2014;Baek et al. 2017).”
What the sources say
- Not checked yetcites Itoh et al. 2013
- Not checked yetcites Park et al. 2014
- Not checked yetcites Baek et al. 2017
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
“This protein is important for mitochondrial quality surveillance and induces mitochondrial fission, which as a consequence reduces the protein levels of mitofusin (MFN) 1/2 and optic atrophy type 1 (OPA1); GTPases that promote the fusion process (Baek et al. 2017).”
What the sources say
- Not checked yetcites Baek et al. 2017
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
“Furthermore, AMPK inhibition promotes a reduction of GLUT3 and GLUT4 in plasma membranes of hippocampal neurons, reducing ATP production (da Silva et al. 2017).”
What the sources say
- Not checked yetcites da Silva et al. 2017
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
“Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by a loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and the presence of Lewy bodies (with a-synuclein inclusions) in the substantia nigra (Sveinbjornsdottir 2016).”
What the sources say
- Not checked yetcites Sveinbjornsdottir 2016
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.
None of the sources cited for this claim have been checked yet.
In the paper
“As dysfunctions in cerebral energy metabolism are considered a hallmark of AD, their detection represents a tool for AD diagnosis and understanding of pathophysiological mechanisms (Ferris et al. 1980;Mosconi 2013).”
What the sources say
- Not checked yetcites Ferris et al. 1980
- Not checked yetcites Mosconi 2013
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.
None of the sources cited for this claim have been checked yet.
In the paper
“As aging is a major risk factor for the onset of neurodegenerative diseases like AD, the mitochondrial cascade hypothesis (Swerdlow and Khan 2004) suggests that accumulated mutations in mtDNA caused by ROS play a pivotal role in mitochondrial dysfunction (Lin and Beal 2006), which can be an early event in AD (Nunomura et al. 2001).”
What the sources say
- Not checked yetcites Swerdlow and Khan 2004
- Not checked yetcites Lin and Beal 2006
- Not checked yetcites Nunomura et al. 2001
hedgeddirect- 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 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
“Diabetic conditions can have a disease-modifying effect for progressive neurodegenerative disorders of the brain like Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, or multiple sclerosis, all of which involve diverse molecular and cellular mechanisms, yet despite unrelated aetiology, they all share a metabolic component which may be a consequence of the disorder or even”
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
“Diabetic conditions can have a disease-modifying effect for progressive neurodegenerative disorders of the brain like Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, or multiple sclerosis, all of which involve diverse molecular and cellular mechanisms, yet despite unrelated aetiology, they all share a metabolic component which may be a consequence of the disorder or even”
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Additionally, Ab oligomers reduce hexokinase activity and ATP levels in neuronal cultures (da Silva et al. 2017).”
What the sources say
- Not checked yetcites da Silva et al. 2017
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
“Interestingly, in a large retrospective cohort study, a higher prevalence of PD in patients with T2DM was detected (De Pablo-Fernandez et al. 2018).”
What the sources say
- Not checked yetcites De Pablo-Fernandez et al. 2018
plaincorrelational- 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
“This technique has revealed a marked reduction in FDG labeling that correlates with AD progression and is more prominent in brain areas most affected by the disease, including the temporal and occipital lobes (Marcus et al. 2014).”
What the sources say
- Not checked yetcites Marcus et al. 2014
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.
In the paper
“Axonal energy failure and disrupted mitochondrial energetics, especially in white matter astrocytes, have been implicated in MS (Cambron et al. 2012), highlighted by the absence of b2-adrenoreceptors in the astrocytes of MS patients (Cambron et al. 2012), which impairs the noradrenaline-mediated glycogenolysis necessary to exploit this energy reservoir for neurons and their axons, thus leading to”
What the sources say
- Not checked yetcites Cambron et al. 2012
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.
In the paper
“Axonal energy failure and disrupted mitochondrial energetics, especially in white matter astrocytes, have been implicated in MS (Cambron et al. 2012), highlighted by the absence of b2-adrenoreceptors in the astrocytes of MS patients (Cambron et al. 2012), which impairs the noradrenaline-mediated glycogenolysis necessary to exploit this energy reservoir for neurons and their axons, thus leading to”
What the sources say
- Not checked yetcites Cambron et al. 2012
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
“Intra-axonal accumulation of calcium activates phospholipases and proteases like calpain, which bring about axonal disintegration, and further leads to energy failure via mitochondrial disruption (Pennisi et al. 2011).”
What the sources say
- Not checked yetcites Pennisi et al. 2011
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.
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 following long-term depression of cerebral metabolic rate of glucose, indicating reduced glucose uptake and utilization, suggests the inability of the injured brain to meet the increased metabolic demands which could be due to reduced glucose supply (as a consequence of hindered cerebral blood flow, CBF), defects in glucose transporter systems, and/or reduced need for glucose.”
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.
None of the sources cited for this claim have been checked yet.
In the paper
“However, changes in CBF in patients with TBI show a strong heterogeneity with some patients showing significantly reduced CBF, while in others, normal CBF values can be seen that persist for days to weeks after injury (Bouma et al. 1991;Marion et al. 1991).”
What the sources say
- Not checked yetcites Bouma et al. 1991
- Not checked yetcites Marion et al. 1991
boosted- 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.
In the paper
“These metabolic defects, which comprise also disrupted metabolic interactions between neurons and glial cells (reviewed in Tefera and Borges 2017), result in impaired mitochondrial oxidative phosphorylation, declined generation of ATP, and subsequent death of neurons as well as non-neuronal cells.”
What the sources say
- Not checked yetcites Tefera and Borges 2017
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Studies in various animal models of PD reveal that mitochondrial dysfunction in the brain is linked to alterations in mitochondrial morphology, dynamics, mutation of mtDNA, increased proton leak (Villeneuve et al. 2016), and decreased rates of electron transfer (Golpich et al. 2017;van der Merwe et al. 2017).”
What the sources say
- Not checked yetcites Villeneuve et al. 2016
- Not checked yetcites Golpich et al. 2017
- Not checked yetcites van der Merwe et al. 2017
plaincorrelational- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Structural damage causes reduced cerebral blood flow and cell membrane disruption and is accompanied by mitochondrial dysfunction, inflammatory responses and oxidative stress, ionic gradient breakdown, glutamate-mediated excitotoxicity, stress signaling, and ultimately cell death (Lo et al. 2003;Malik and Dichgans 2018).”
What the sources say
- Not checked yetcites Lo et al. 2003
- Not checked yetcites Malik and Dichgans 2018
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.
It may state two separate claims as one.
In the paper
“These impairments in mitochondria are associated with: accumulation of oxidation products of phospholipids and proteins, increased ROS production, increased lipid peroxidation, decreased respiration and membrane potential, decreased capacity for ATP production, and neuronal degeneration due to oxidative damage and energy defects in the aged mammalian brain (Navarro and Boveris 2010).”
What the sources say
- Not checked yetcites Navarro and Boveris 2010
plaincorrelational- 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.
In the paper
“Moreover, altered mitochondrial fission may result in synaptic loss and DA neuronal cell loss (Berthet et al. 2014).”
What the sources say
- Not checked yetcites Berthet et al. 2014
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.
In the paper
“Altered ionic balance results in a calcium influx (Kitchen et al. 2015b), which in turn leads to the depolarization of the mitochondrial membrane due to the opening of the mitochondrial permeability transition pore and cytochrome cmediated caspase-dependent apoptosis.”
What the sources say
- Not checked yetcites Kitchen et al. 2015b
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.
It may state two separate claims as one.
In the paper
“DA neurons lacking the mitochondrial fusion gene MFN2 display fragmented mitochondria and their transport within the axon is hindered (Anh et al. 2012).”
What the sources say
- Not checked yetcites Anh et al. 2012
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.
It may state two separate claims as one.
In the paper
“These metabolic substrates were able to modify ALS disease progression to varying degrees, signifying the contribution of CNS energy metabolism toward the pathogenesis of the disease and the need for further studies to correct metabolic defects.”
What the sources say
- Not checked yetcites Tefera and Borges 2017
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
“It is postulated that the acute phase of hyperglycolysis occurs in order to compensate the increased cellular energy requirement to restore the ionic imbalance and membrane potential (Karelina and Weil 2016).”
What the sources say
- Not checked yetcites Karelina and Weil 2016
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Several pathogenic mechanisms are believed to contribute to motor neuron death, including abnormal protein aggregation (Bruijn et al. 1997), oxidative stress (Barber et al. 2006), glutamate excitotoxicity (Rothstein 1995), and impaired energy metabolism (Dupuis et al. 2011).”
What the sources say
- Not checked yetcites Bruijn et al. 1997
- Not checked yetcites Barber et al. 2006
- Not checked yetcites Rothstein 1995
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Numerous preclinical investigations in vitro and in vivo as well as in patients have revealed metabolic irregularities in ALS brains which include reductions in glucose uptake (Miyazaki et al. 2012) and reduced gene expression of enzymes involved in glycolysis (Ferraiuolo et al. 2011), PPP (Kirby et al. 2005), and TCA cycle (D'Arrigo et al. 2010), as well as the ETC (Ferraiuolo et al. 2011).”
What the sources say
- Not checked yetcites Miyazaki et al. 2012
- Not checked yetcites Ferraiuolo et al. 2011
- Not checked yetcites Kirby et al. 2005
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 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
“Functionally, energy crisis-driven impaired ATP generation may lead to the failure of important pumps and exchangers like the Na + /K + -ATPase maintaining the Na + concentration within the axon, which is ATP dependent, and the Na + /Ca 2+ exchanger, which further sustains calcium homeostasis.This leads to an increased Na + and Ca 2+ influx in axons and disrupted membrane potential.”
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
“Moreover, neurodegenerative disorders are not exclusively restricted to neurons but glial cells are indeed a pivotal player.”
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. 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
“TBI is frequently accompanied by ischemia and hypoxia, major but not the only causes of mitochondrial dysfunction after injury (Carpenter et al. 2015;Patet et al. 2016).”
What the sources say
- Not checked yetcites Carpenter et al. 2015
- Not checked yetcites Patet et al. 2016
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.
It may state two separate claims as one.
In the paper
“GLUT1 expression in human brain was found to be much higher as compared to chimpanzee and macaque brains, but GLUT4 expression is higher in chimpanzee skeletal muscle than in human and macaque muscle.”
What the sources say
- Not checked yetcites Pfefferle et al. 2011
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Some studies connected the possibility of having such a costly brain with the relative reduction of gut (Aiello and Wheeler 1995) or skeletal muscles (Leonard et al. 2003) in volume or with the decrease of energy spent on locomotive tasks (Navarrete et al. 2011).”
What the sources say
- Not checked yetcites Aiello and Wheeler 1995
- Not checked yetcites Leonard et al. 2003
- Not checked yetcites Navarrete et al. 2011
hedgedcorrelational- 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 existence of many alternative energy sources to fuel the brain as well as the pathological consequences of disturbed regional/global brain metabolism and energetics highlight the importance of maintaining brain energy homeostasis.”
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
“The expression of the active creatine transporter SLC6A8 and the brain-type cytosolic creatine kinase are higher in humans than in chimpanzees and rhesus macaques in cerebral cortex and cerebellum, but not in skeletal muscles (Pfefferle et al. 2011).”
What the sources say
- Not checked yetcites Pfefferle et al. 2011
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.
The paper relies on this without support.
K+ is released at nodes of Ranvier during AP propagation, at serotonergic synapses, or at the cholinergic neuromuscular junction.
“as K + is released not only by the postsynaptic terminal during glutamatergic neurotransmission but also at nodes of Ranvier during AP propagation, at serotonergic synapses, or at the cholinergic neuromuscular junction.”
The paper relies on this without support.
Uptake of extracellular glutamate is expensive as astrocytes utilize one ATP for the transfer of one glutamate.
“Uptake of extracellular glutamate is an expensive process as astrocytes utilize one ATP for the transfer of one glutamate.”
The authors state this as an assumption.
Lactate secreted by astrocytes through MCT1 and MCT4 is transported by MCT2 into neurons, where it can be converted to pyruvate.
“Hence, lactate secreted by astrocytes through MCT1 and MCT4 is assumed to be transported by MCT2 into neurons, where it can be converted to pyruvate (Fig. 2).”
The paper relies on this without support.
Energy homeostasis is essential in maintaining a healthy state of the brain.
“Energy homeostasis is essential in maintaining a healthy state of the brain.”
The paper relies on this without support.
Microglia and macrophages within the CNS have a high energetic demand to function as they monitor for abnormalities and make connections with neurons.
“Microglia and macrophages within the CNS have a high energetic demand to function as they monitor for abnormalities and make connections with neurons.”
The paper relies on this without support.
The three major energy substrates in microglia are glucose, fatty acids, and glutamine.
“The three major energy substrates in microglia are glucose, fatty acids, and glutamine.”
The paper relies on this without support.
Disrupted energy homeostasis may either be a cause or an effect of a disease or a disease-like condition (i.e., unhealthy aging).
“Disrupted energy homeostasis may either be a cause or an effect of a disease or a disease-like condition (i.e., unhealthy aging).”
The paper relies on this without support.
Metabolic changes not only contribute to the pathology of neurodegenerative diseases, traumatic brain injury, or stroke but also cause neurological symptoms of diabetes mellitus, and accompany normal aging.
“Metabolic changes not only contribute to the pathology of neurodegenerative diseases, traumatic brain injury, or stroke but also cause neurological symptoms of diabetes mellitus, and accompany normal aging.”
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
“In the brain, ATP is required for neurotransmitter synthesis, protein turnover, neurotransmission, transport, and maintenance of ion gradients [119].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [119]
Experimental — accuracy not yet measuredIn the citing paper
“However, when glucose availability is reduced, the brain can use alternative energy substrates such as lactate, medium-chain triglycerides and ketone bodies [30].”
From Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence (2020) · cites this paper as [30]
Citations
Cites
1 retracted
RETRACTED: Redox regulation of cellular stress response in multiple sclerosis
Pennisi, G., Cornelius, C., Cavallaro, M., Salinaro, A. T., Cambria, M. T., Pennisi, M., Bella, R., Milone, P., Ventimiglia, B., Migliore, M. R., et al. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.07.092 · Cited by 65 · cited 1×
“Intra-axonal accumulation of calcium activates phospholipases and proteases like calpain, which bring about axonal disintegration, and further leads to energy failure via mitochondrial disruption (Pennisi et al. 2011).”
BackgroundRetractedMitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455
Sokoloff, L., Reivich, M., Kennedy, C., Rosiers, M. H. D., Patlak, C. S., Pettigrew, K. D., Sakurada, O., & Shinohara, M. (1977) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1977.tb10649.x · Cited by 6,000 · cited 1×
“The human brain, however, accounts for 20% of oxygen (O2) consumption and 25% of glucose utilization, although it amounts to only 2% of body weight (Sokoloff et al. 1977).”
BackgroundTreatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia
Bernard, S. A., Gray, T. W., Buist, M., Jones, B. M., Silvester, W., Gutteridge, G. A., & Smith, K. L. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa003289 · Cited by 5,388
Kettenmann, H., Hanisch, U.-K., Noda, M., & Verkhratsky, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00011.2010 · Cited by 3,547 · cited 3×
“In their resting state, microglia act as the CNS’s surveillance system, equipped with a wide range of receptors (i.e., neurotransmitter, cytokine, chemokine, pattern recognition) (Kettenmann et al. 2011).”
BackgroundAn Energy Budget for Signaling in the Grey Matter of the Brain
Attwell, D., & Laughlin, S. B. (2001) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200110000-00001 · Cited by 3,543 · cited 12×
“The residual energy expenditure persisting after the suppression of spiking and/or Na+/K+-ATPase was attributed to non-signaling, or ‘housekeeping’, processes (Attwell and Laughlin 2001; Du et al., 2008; Harris and Attwell 2012; Engl and Atwell 2015).”
BackgroundMethodInfluentialPellerin, L., & Magistretti, P. J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.22.10625 · Cited by 2,927 · cited 8×
“Astrocytes are the most abundant glial cells in the brain and display a number of active roles critical for CNS function (Nedergaard et al. 2003; Barros et al. 2018b), including regulation of neurotransmitters (Anderson and Swanson 2000), supplying substrates to neurons for OxPhos (Pellerin et al. 1998), maintaining w…”
BackgroundResultInfluentialWhole-body hypothermia for neonates with hypoxic-ischemic encephalopathy
Shankaran, S., Laptook, A. R., Ehrenkranz, R. A., Tyson, J. E., McDonald, S. A., Donovan, E. F., Fanaroff, A. A., Poole, W. K., Wright, L. L., Higgins, R. D., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmcps050929 · Cited by 2,862
Tripartite synapses: glia, the unacknowledged partner
Araque, A., Parpura, V., Sanzgiri, R. P., & Haydon, P. G. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(98)01349-6 · Cited by 2,529 · cited 3×
“Additionally, astrocytes play a major role in synapse formation, maintenance, and plasticity during brain development and in adulthood (Araque et al. 1999; Han et al. 2013; Kim et al. 2017).”
BackgroundBrain 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×
“Thus, high expression and activity of PFK in astrocytes results in glucose and glucose6-phosphate (G6P) mainly being metabolized via the glycolytic pathway (B elanger et al. 2011).”
Background
Research works printed but not linked: 2
- 10.1242/jeb.02208 · DOI
- Silva G. S. S., 2017, Amyloid‐β oligomers transiently inhibit AMP‐activated kinase and cause metabolic defects in hippocampal neurons, J. Biol. Chem., 116, 753525
Cited by
Sorted by citations
Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing
Cunnane, S. C., Trushina, E., Morland, C., Prigione, A., Casadesus, G., Andrews, Z. B., Beal, M. F., Bergersen, L. H., Brinton, R. D., de la Monte, S., et al. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0072-x · Cited by 1,003
Tardy, A.-L., Pouteau, E., Marquez, D., Yilmaz, C., & Scholey, A. (2020) · Nutrients · doi:10.3390/nu12010228 · Cited by 541
“However, when glucose availability is reduced, the brain can use alternative energy substrates such as lactate, medium-chain triglycerides and ketone bodies [30].”
BackgroundEffects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases
Jensen, N. J., Wodschow, H. Z., Nilsson, M., & Rungby, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228767 · Cited by 450
Targeting Aquaporin-4 Subcellular Localization to Treat Central Nervous System Edema
Kitchen, P., Salman, M. M., Halsey, A. M., Clarke-Bland, C., MacDonald, J. A., Ishida, H., Vogel, H. J., Almutiri, S., Logan, A., Kreida, S., et al. (2020) · Cell · doi:10.1016/j.cell.2020.03.037 · Cited by 452
“It is rapidly triggered when a state of hypoxia causes loss of energy-dependent solute homeostasis (Bordone et al., 2019).”
Self-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
“Since dysfunctional brain energy metabolism is implicated in several neurodegenerative diseases (Beal, 1992; Bordone et al., 2019; Camandola and Mattson, 2017; Choi, 1988), cellular glutamate metabolism is a growing area of interest in neurodegenerative disease research (Cunnane et al., 2020;…”
Self-citation
Metadata
- Authors
- Bordone, M. P., Salman, M. M., Titus, H. E., Amini, E., Andersen, J. V., Chakraborti, B., Diuba, A. V., Dubouskaya, T. G., Ehrke, E., Espindola de Freitas, A., Braga de Freitas, G., Gonçalves, R. A., Gupta, D., Gupta, R., Ha, S. R., Hemming, I. A., Jaggar, M., Jakobsen, E., Kumari, P., Lakkappa, N., Marsh, A. P. L., Mitlöhner, J., Ogawa, Y., Paidi, R. K., Ribeiro, F. C., Salamian, A., Saleem, S., Sharma, S., Silva, J. M., Singh, S., Sulakhiya, K., Tefera, T. W., Vafadari, B., Yadav, A., Yamazaki, R., & Seidenbecher, C. I.
- Affiliations
- Universidad de Buenos Aires (AR)
- Boston Children's Hospital (US)
- Northwestern University (US)
- University Kebangsaan Malaysia Medical Centre (MY)
- University of Copenhagen (DK)
- Manovikas Kendra Rehabilitation and Research Institute (IN)
- Lomonosov Moscow State University (RU)
- National Academy of Sciences of Belarus (BY)
- University of Bremen (DE)
- Neurobiology Section Biological Sciences Division University of California San Diego, La Jolla California USA
- Institute of Medical Biochemistry Federal University of Rio de Janeiro Rio de Janeiro Brazil
- Queen's University (CA)
- Birla Institute of Technology and Science, Pilani (IN)
- Indian Institute of Toxicology Research (IN)
- Baylor College of Medicine (US)
- The University of Western Australia (AU)
- Tata Institute of Fundamental Research (IN)
- Defence Research and Development Organisation (IN)
- JSS College of Pharmacy (IN)
- Royal Children's Hospital (AU)
- Leibniz Institute for Neurobiology (DE)
- Jikei University School of Medicine (JP)
- Indian Institute of Chemical Biology (IN)
- Universidade Federal do Rio de Janeiro (BR)
- Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
- University of Minho (PT)
- Indira Gandhi National Tribal University (IN)
- The University of Queensland (AU)
- Technical University of Munich (DE)
- Tokyo University of Pharmacy and Life Sciences (JP)
- Center for Behavioral Brain Sciences (DE)
- Corresponding author
- Seidenbecher, Constanze I.
- ORCID
- Bordone, Melina Paula
- Salman, Mootaz M.
- Titus, Haley E.
- Amini, Elham
- Andersen, Jens V.
- Diuba, Artem V.
- Gonçalves, Rafaella A.
- Gupta, Richa
- Hemming, Isabel A.
- Jaggar, Minal
- Jakobsen, Emil
- Lakkappa, Navya
- Marsh, Ashley P. L.
- Mitlöhner, Jessica
- Ogawa, Yuki
- Paidi, Ramesh Kumar
- Ribeiro, Felipe C.
- Salamian, Ahmad
- Sharma, Sorabh
- Silva, Joana M.
- Singh, Shripriya
- Sulakhiya, Kunjbihari
- Tefera, Tesfaye Wolde
- Vafadari, Behnam
- Yadav, Anuradha
- Yamazaki, Reiji
- Seidenbecher, Constanze I.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2019-09-10
- Volume
- 151
- Issue
- 2
- Pages
- 139-165
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2964281414
- Semantic Scholar
- d9e216030a3b4d892a19f367b66743386c20611d
- Cited by
- 205
- References
- 331
- Citations by year
- 2026: 14 · 2025: 31 · 2024: 16 · 2023: 25 · 2022: 33 · 2021: 53 · 2020: 29 · 2019: 4
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-03-09)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neurochemistry (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-nd)
- OPUS (Augsburg University) (submittedVersion, cc-by-nc-nd)
- UWA Profiles and Research Repository (UWA) (submittedVersion, cc-by-nc-nd)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion, other-oa)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by-nc-nd)
- Funders
- Deutsche Forschungsgemeinschaft (RTG2413, SFB 779)
- Bundesministerium für Bildung und Forschung
- Lundbeckfonden (R249-2017-109)
- International Society for Neurochemistry
- European Social Fund (ZS/2016/08/80645)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- brain energy metabolism, mitochondrial quality control, neurotransmission, synaptic plasticity, glucose metabolism, glutamate, lactate, ketone bodies, medium-chain fatty acids, astrocytes, pericytes, microglia, energy homeostasis, central nervous system disorders
- MeSH terms
- Animals, Astrocytes, Brain, Congresses as Topic, Energy Metabolism, Humans, Neurochemistry, Neuroglia, Neurons, Students
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 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
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