The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index; 16 of the 27 sources its claims cite were checked for support.
Aerobic Glycolysis in the Human Brain Is Associated with Development and Neotenous Gene Expression
Open accessAbstract
Aerobic glycolysis (AG; i.e., nonoxidative metabolism of glucose despite the presence of abundant oxygen) accounts for 10%-12% of glucose used by the adult human brain. AG varies regionally in the resting state. Brain AG may support synaptic growth and remodeling; however, data supporting this hypothesis are sparse. Here, we report on investigations on the role of AG in the human brain. Meta-analysis of prior brain glucose and oxygen metabolism studies demonstrates that AG increases during childhood, precisely when synaptic growth rates are highest. In resting adult humans, AG correlates with the persistence of gene expression typical of infancy (transcriptional neoteny). In brain regions with the highest AG, we find increased gene expression related to synapse formation and growth. In contrast, regions high in oxidative glucose metabolism express genes related to mitochondria and synaptic transmission. Our results suggest that brain AG supports developmental processes, particularly those required for synapse formation and growth.
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Claims the paper makes
16 of 27 cited sources checked · 5 supported · 0 flagged · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Aerobic glycolysis (AG), i.e., non-oxidative metabolism of glucose despite the presence of abundant oxygen, accounts for 10–12% of glucose used by the adult human brain.”
- Also stated in: § INTRODUCTION · hedged
“approximately 10–12% of the total glucose consumed by a normal adult brain (CMRglc) is in excess of oxygen consumption (CMRO2)”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > Abstract
What the sources say
- Partly supportedcites Boyle et al., 1994 sourceExperimental — accuracy not yet measured
The Results report an oxygen-to-glucose metabolism ratio of 5.33 during sleep, consistent with roughly 11% of glucose not being oxidized if complete oxidation requires a ratio of 6. But the presleep ratio was 4.85, and the paper does not state that aerobic glycolysis generally accounts for 10–12% of glucose use in the adult human brain. (LLM, conf=0.83)
- Partly supportedcites Madsen et al., 1995 sourceExperimental — accuracy not yet measured
In “Global metabolism before and during mental activation” (page unavailable), the paper reports a 12% increase in glucose uptake during activation, not that aerobic glycolysis accounts for 10–12% of glucose use in the normal resting adult brain. Its baseline lactate/glucose index was 6%, and the Concluding remarks say the data do not establish the nature of the metabolic processes behind the altered oxygen/glucose ratio. (LLM, conf=0.87)
- Supportedcites Vaishnavi et al., 2010 source
The paper defines aerobic glycolysis as glucose metabolism beyond that used for oxidative phosphorylation despite sufficient oxygen (opening text in our copy). The Discussion states that aerobic glycolysis accounts for 10–12% of glucose consumed in the adult brain. (LLM, conf=0.93)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § INTRODUCTION · hedged
Every source the paper cites for this claim was checked and supports it.
In the paper
“AG varies regionally in the resting state.”
- Also stated in: § INTRODUCTION · plain
“In the resting adult human brain, AG varies regionally”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > Abstract
What the sources say
- Supportedcites Vaishnavi et al., 2010 source
The Abstract reports PET measurements of aerobic glycolysis in 33 neurologically normal young adults at rest and describes differences among brain regions. The Results section, “Resting Aerobic Glycolysis,” identifies regions with significantly elevated and significantly low levels. (LLM, conf=0.95)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § INTRODUCTION · plain
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“AG correlates with centrality as defined by large scale, structural and resting state function connectivity studies of the human brain”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites Bullmore and Sporns, 2012 source
- Partly supportedcites Vaishnavi et al., 2010 sourceExperimental — accuracy not yet measured
The Results report that regions with elevated aerobic glycolysis overlap the default-mode and control systems mapped using resting-state functional MRI. The paper does not report a correlation with network centrality or assess centrality defined by structural connectivity; its Methods describe the comparison as qualitative. (LLM, conf=0.87)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesEvery source the paper cites for this claim was checked and supports it.
In the paper
“For the 116 AG-related genes, an independent gene ontology tool, GeneMANIA.org, confirmed that these genes are associated with neuronal projections and axonal and dendritic development”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > RESULTS > AG is related to spatially specific gene expression
What the sources say
- Supportedcites Warde-Farley et al., 2010 source
The Abstract identifies GeneMANIA.org as a tool for analyzing gene lists and predicting gene function, and the Introduction describes how it displays functional associations for a user's gene list. The citation supports the identification of the tool; the result for the 116 AG-related genes is the citing authors' analysis, not a result reported in this source paper. (LLM, conf=0.88)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Interestingly, in the adult brain, the highest levels of resting state AG are found in the default mode network (DMN)”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > DISCUSSION
What the sources say
- Partly supportedcites Raichle et al., 2001 sourceExperimental — accuracy not yet measured
The opening section describes a baseline default mode in the resting adult brain, and the Discussion identifies areas that may be tonically active in that state. But the paper examines oxygen extraction and task-related activity decreases; it does not report aerobic glycolysis levels or establish that they are highest in those areas (searched: aerobic glycolysis, glycolysis, glucose). (LLM, conf=0.82)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Curiously, AG persists for at least 40 minutes following cognitive demanding task performance, despite the return of blood flow and lactate production to control levels”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites Fox et al., 1988 source
- Partly supportedcites Madsen et al., 1995 sourceExperimental — accuracy not yet measured
The Global metabolism section (page unavailable) reports that glucose uptake remained elevated relative to oxygen uptake for about 40 minutes after the mental task. The Relation between excess CMRglc and CMRlac section says lactate measures returned to baseline within 20 minutes. But the Concluding remarks (page unavailable) say the study cannot identify the metabolic process behind the persistent uptake-ratio change, so it does not establish persistent aerobic glycolysis; the passages also do not establish that blood flow returned to control levels after the task. (LLM, conf=0.88)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“The DMN also constitutes a central hub of structural (axonal) connectivity”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Bullmore and Sporns, 2012 source
- Could not verifycites Vaishnavi et al., 2010 sourceExperimental — accuracy not yet measured
The Results describe the DMN using resting-state fMRI correlations, and the Methods compare those functional maps with aerobic glycolysis. Searches for structural or axonal connectivity and hub status found no passage in our copy establishing that the DMN is a central hub of structural connectivity. (LLM, conf=0.76)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In resting adult humans, AG correlates with persistence of gene expression typical of infancy (transcriptional neoteny).”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe 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
“In contrast, regions high in oxidative glucose metabolism express genes related to mitochondria and synaptic transmission.”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AG increases during childhood, precisely when synaptic growth rates are highest.”
- Also stated in: § Meta-analysis of prior studies of brain glucose and oxygen consumption · boosted
“AG increases dramatically during childhood”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Synaptic growth rates are highest during early childhood.
- Also stated in: § Meta-analysis of prior studies of brain glucose and oxygen consumption · boosted
- Probably not a substantial claim. 16
- It may state two separate claims as one. 15
Every source the paper cites for this claim was checked and supports it.
In the paper
“AG and the oxygen-glucose index (OGI) are nearly perfectly inversely correlated (r = −0.98) (Vaishnavi et al., 2010).”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > EXPERIMENTAL PROCEDURES > Brain PET data analysis and regional alignment to gene expression data
What the sources say
- Supportedcites Vaishnavi et al., 2010 source
The Results (Table 2) report a correlation of −0.986 between the glycolytic index (GI) and OGI across Brodmann regions. The Results define GI as a measure of aerobic glycolysis, so the claimed near-perfect inverse correlation is supported; −0.98 is an approximation of the reported value. (LLM, conf=0.92)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“More specifically, we hypothesize that AG supports synaptic and neurite formation, as well as turnover, which likely persists throughout the lifespan”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > DISCUSSION
What the sources say
- Partly supportedcites Goyal and Raichle, 2013 sourceExperimental — accuracy not yet measured
The Discussion speculates that aerobic glycolysis may coincide with high synaptic growth rates in early childhood, and the Abstract reports model-based evidence of ongoing synaptic turnover in the adult human cortex. The paper does not establish that aerobic glycolysis supports synaptic or neurite formation and turnover throughout the lifespan. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites Marder and Goaillard, 2006 source
Tests✗ Asserted: fails✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. The authors may not put it forward as true. It may state two separate claims as one.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“we found that the 116 AG-related genes are also enriched for neuron specific markers, genes downregulated in Alzheimer disease and aging, genes associated with autism, and proteins found in the human post-synaptic density”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > RESULTS > AG is related to spatially specific gene expression
What the sources say
- Could not verifycites Langfelder and Horvath, 2008 sourceExperimental — accuracy not yet measured
The Results > Mouse Data Application section reports enrichment for gene modules associated with mouse body weight, not for 116 aerobic-glycolysis-related genes. Searches for those genes, neuron-specific markers, autism, and post-synaptic density found no passage addressing the claimed enrichment. (LLM, conf=0.76)
- Not matchedcites Li et al., 2007
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“The AHBA data were corrected for batch effects and normalized to the 75% quantile, as previously described (Hawrylycz et al., 2012). BSS data also were quantile normalized.”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > EXPERIMENTAL PROCEDURES > Preprocessing of brain gene expression data
What the sources say
- Could not verifycites Hawrylycz et al., 2012 sourceExperimental — accuracy not yet measured
The Methods sections on Sample processing and Microarray data analysis describe how the AHBA microarrays were generated and analyzed, but do not specify batch-effect correction or normalization to the 75th quantile. Searches for “batch effect,” “quantile,” and “75% quantile” found no passage establishing those steps. The citation is attached to the AHBA statement; the separate BSS normalization statement is not attributed to this source. Page numbers were not available in our copy. (LLM, conf=0.72)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“AG is a prominent feature of cancer cell metabolism; its main role is thought to be support of biosynthetic pathways required for cellular proliferation”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > INTRODUCTION
What the sources say
- Partly supportedcites Locasale and Cantley, 2011 sourceExperimental — accuracy not yet measured
The Warburg Effect and cell growth section describes aerobic glycolysis as a common feature of tumor cells and identifies support of biosynthesis as one of its functions. It also says those functions are multiple and debated, including redox balance, energy balance, and signaling; it does not identify biosynthesis as the main role. No page number is available in our copy. (LLM, conf=0.88)
- Supportedcites Lunt and Vander Heiden, 2011 source
The Introduction describes aerobic glycolysis in a wide variety of tumors. The section “A major function of aerobic glycolysis is to support macromolecular synthesis” says its major function in proliferating cells is to maintain glycolytic intermediates as precursors for macromolecules. The claim preserves the paper’s qualified framing by saying this role is “thought to be” the main one. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“nearly 25% of resting glucose consumption is non-oxidative in the medial prefrontal gyrus, while AG comprises only 2% of glucose consumption in the cerebellum”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > INTRODUCTION
What the sources say
- Partly supportedcites Vaishnavi et al., 2010 sourceExperimental — accuracy not yet measured
The Results (Table 1; page unavailable) report elevated aerobic glycolysis in the prefrontal cortex and low levels in the cerebellum. Using the Results’ stated OGI benchmark of 6, the table’s values imply about 23% non-oxidative glucose use in the prefrontal cortex, close to 25%, but about 1% in the cerebellum rather than 2%. The table reports prefrontal cortex, not a specific value for the medial prefrontal gyrus. (LLM, conf=0.86)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was no significant enrichment of genes related to glycolysis or genes regulated by agonal stress”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > RESULTS > AG is related to spatially specific gene expression
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We find that OGI is approximately 5 during the fetal period, decreases to less than 4 during early childhood, progressively rises to 5.67 in young and mid-age adults, and ultimately exceeds 6 in older adults”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > RESULTS > Meta-analysis of prior studies of brain glucose and oxygen consumption
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During the early fetal period, there is little differential regional expression. Postnatally, cerebellar expression (the area in the adult brain with the lowest level of AG, see Figure 1) falls while cortical expression continues to rise.”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > RESULTS > AG is related to spatially specific gene expression
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that the 116 glycolytic genes collectively exhibit a unique expression pattern across the lifespan (Figure 4a) that strikingly varies across the brain.”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > RESULTS > AG is related to spatially specific gene expression
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Regions with high AG were found to cluster independently from regions with low AG along the y-axis (principle coordinate 2) in the resulting plot while, for example, high versus low OEF regions separated along the x-axis (principle coordinate 1)”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > RESULTS > Comparison of AG related brain gene expression to CMRglc and other metabolic measures
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“resting cerebral blood flow tracks glucose utilization during childhood, but then tracks oxygen consumption during adulthood”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > RESULTS > Meta-analysis of prior studies of brain glucose and oxygen consumption
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We further compared these measurements to a similar set of PET measurements in FreeSurfer-derived regions matched to the BSS regional nomenclature, and found only slight differences.”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > EXPERIMENTAL PROCEDURES > Brain PET data analysis and regional alignment to gene expression data
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“since the cerebellum shows the lowest AG amongst all brain regions assessed in the BSS.”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > EXPERIMENTAL PROCEDURES > Calculation of regional transcriptional neoteny
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Donor brains with post-mortem intervals >24 hours or with >25% of microarray samples with an RNA integrity index (RIN) less than 7.5 were excluded to maximize the integrity of our analysis.”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > EXPERIMENTAL PROCEDURES > Preprocessing of brain gene expression data
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Hence, data from only one of the AHBA donors was used, since only this brain met our stringent RNA integrity and post-mortem interval criteria.”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > EXPERIMENTAL PROCEDURES > Preprocessing of brain gene expression data
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
In the paper
“More recently, the DMN has emerged as among the most functionally robust networks in the brain as evidenced by its correlated intrinsic activity”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Fox and Raichle, 2007 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Another caveat is that gene expression levels may only modestly correlate with protein and enzyme levels because of post-transcriptional modifications.”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > DISCUSSION
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
- Rests on an assumption: Gene expression levels are a valid proxy for regional functional and molecular processes such as synaptic growth.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, our results do not address causation.”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the available data demonstrate that brain AG peaks (OGI is at a minimum) precisely when synaptic development peaks in the human brain, i.e., during early childhood.”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > RESULTS > Meta-analysis of prior studies of brain glucose and oxygen consumption
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Synaptic growth rates are highest during early childhood.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The meta-analysis reported in Figure 2 was based on in-depth review of the literature, using Pubmed, Google Scholar, and reference lists in several papers identifying studies that measured glucose or oxygen metabolism over the whole brain or cerebral cortex.”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > EXPERIMENTAL PROCEDURES > Meta-analysis of brain metabolism across the lifespan
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To evaluate the significance of this finding, the same analysis was performed after repeatedly shuffling the AG values among the 16 BSS regions to measure the percentage of instances that produced an equivalent number of genes as compared to the actual AG values (AHBA was excluded from this permutation analysis given the difficulty in relating shuffled BSS AG values to the AHBA regions).”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > EXPERIMENTAL PROCEDURES > Regional comparative analysis of the brain PET and gene expression data
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
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
“Thus, our analyses link AG to synaptic and neurite growth and formation but do not elucidate the specific mechanisms by which this occurs.”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
In the paper
“Similarly, brain AG was previously found to be highest in regions most vulnerable to amyloid deposition”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Vlassenko et al., 2010 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Indeed, upregulation of PDK3 acts as a switch for aerobic glycolysis in certain cancer cell lines”
§ Aerobic glycolysis in the human brain is associated with development and neotenous gene expression > RESULTS > AG is related to spatially specific gene expression
What the sources say
- Not matchedcites Lu et al., 2008
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
The paper relies on this without support.
Synaptic growth rates are highest during early childhood.
“AG increases during childhood, precisely when synaptic growth rates are highest.”
“Thus, the available data demonstrate that brain AG peaks (OGI is at a minimum) precisely when synaptic development peaks in the human brain, i.e., during early childhood.”
The paper relies on this without support.
Metabolic data from different studies and age groups can be combined into a summary representation across the human lifespan despite different methods.
“The meta-analysis of human brain AG (Figure 2) is based on incomplete data obtained using different methods across studies and age groups.”
The paper relies on this without support.
Regional aerobic glycolysis values measured by PET in resting healthy young adults can be assigned to post-mortem gene expression regions to represent regional aerobic glycolysis.
“we assigned each of the 16 regions an AG value using regional PET imaging data previously obtained by our laboratory in resting, healthy young adults”
“We assigned an AG value to each of the ~900 brain regions sampled in the AHBA brain by measuring the glycolytic index in our PET data at the MNI coordinate provided for each of the AHBA regions.”
The paper relies on this without support.
Gene expression levels are a valid proxy for regional functional and molecular processes such as synaptic growth.
“Another caveat is that gene expression levels may only modestly correlate with protein and enzyme levels because of post-transcriptional modifications.”
The authors state this as an assumption.
A 6:1 stoichiometric relationship between oxygen and glucose consumption holds for the brain.
“assuming a 6:1 stoichiometric relationship between oxygen and glucose consumption”
The paper relies on this without support.
The single AHBA donor used is representative of adult human brain gene expression for the regional analyses.
“Hence, data from only one of the AHBA donors was used, since only this brain met our stringent RNA integrity and post-mortem interval criteria.”
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 cited source says what the claim attributes to it.
In the citing paper
“Recent work shows that glucose uptake outpaces oxygen use in the human brain, and that this imbalance also peaks at the age of greatest glucose uptake in childhood”
From Metabolic costs and evolutionary implications of human brain development (2014) · cites this paper as [28]
The cited source says what the claim attributes to it.
In the citing paper
“pointing to an important role of aerobic glycolysis in support of synaptic proliferation and growth (28,30).”
From Metabolic costs and evolutionary implications of human brain development (2014) · cites this paper as [28]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Self-check results appear here once an independent check has confirmed them.
Cited works that were retracted
Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.
Cites a retracted work: 10.1038/nature07767
InfoThe cited work was retracted on 2023-12-18 (notice 10.1038/s41586-023-06943-3), not before this paper was published (2014-01).
Cited work 10.1038/nature07767 · retracted 2023-12-18 · notice 10.1038/s41586-023-06943-3 · this paper published 2014-01
“Given the present findings, it is intriguing to consider the possibility that amyloid deposition is linked to high rates of synaptic turnover (Bufill et al., 2011; Nikolaev et al., 2009).”
Citations
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1 retracted
RETRACTED ARTICLE: APP binds DR6 to trigger axon pruning and neuron death via distinct caspases
Nikolaev, A., McLaughlin, T., O’Leary, D. D. M., & Tessier-Lavigne, M. (2009) · Nature · doi:10.1038/nature07767 · Cited by 992 · cited 1×
“Given the present findings, it is intriguing to consider the possibility that amyloid deposition is linked to high rates of synaptic turnover (Bufill et al., 2011; Nikolaev et al., 2009).”
RetractedSystematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · cited 4×
“The 116 AGassociated genes were analyzed with three gene ontology methods, including GeneMANIA (Warde-Farley et al., 2010), DAVID (Huang da et al., 2009), and userListEnrichmentR (Miller et al., 2011) (Table 1, see also Tables S3 and S4).”
InfluentialWGCNA: an R package for weighted correlation network analysis
Langfelder, P., & Horvath, S. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-559 · Cited by 27,252
A default mode of brain function
Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., & Shulman, G. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.2.676 · Cited by 12,190 · cited 1×
“Interestingly, in the adult brain, the highest levels of resting state AG are found in the default mode network (DMN), a constellation of brain regions originally identified as most active in the absence of attention-demanding, goal-directed task performance (Raichle et al., 2001).”
Self-citationSpontaneous fluctuations in brain activity observed with functional magnetic resonance imaging
Fox, M. D., & Raichle, M. E. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2201 · Cited by 6,700 · cited 1×
“More recently, the DMN has emerged as among the most functionally robust networks in the brain, as evidenced by its correlated intrinsic activity (Fox and Raichle, 2007), a property now widely referred to as functional connectivity (Bullmore and Sporns, 2012).”
Self-citationWarde-Farley, D., Donaldson, S. L., Comes, O., Zuberi, K., Badrawi, R., Chao, P., Franz, M., Grouios, C., Kazi, F., Lopes, C. T., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq537 · Cited by 4,835 · cited 5×
“Similar results are obtained with other gene ontology tools, including GeneMANIA and userListEnrichment (Table S4) (Miller et al., 2011; Warde-Farley et al., 2010).”
InfluentialAn 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 1×
“Most of this glucose is oxidized in order to supply the large amounts of ATP required to maintain membrane ion gradients and other cellular processes related to synaptic transmission (Attwell and Laughlin, 2001; Lennie, 2003; Raichle and Mintun, 2006; Sibson et al., 1997, 1998).”
The economy of brain network organization
Bullmore, E., & Sporns, O. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3214 · Cited by 3,284 · cited 3×
“The DMN also constitutes a central hub of structural (axonal) connectivity (Bullmore and Sporns, 2012; Vaishnavi et al., 2010).”
An anatomically comprehensive atlas of the adult human brain transcriptome
Hawrylycz, M. J., Lein, E. S., Guillozet-Bongaarts, A. L., Shen, E. H., Ng, L., Miller, J. A., van de Lagemaat, L. N., Smith, K. A., Ebbert, A., Riley, Z. L., et al. (2012) · Nature · doi:10.1038/nature11405 · Cited by 3,083 · cited 5×
“The AHBA data were corrected for batch C effects and normalized to the 75%quantile as previously described (Hawrylycz et al., 2012).”
InfluentialSelf-citationAerobic glycolysis: Meeting the metabolic requirements of cell proliferation
Lunt, S. Y., & Vander Heiden, M. G. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154237 · Cited by 3,057
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Hyperinsulinemic hypoglycemia: clinical, molecular and therapeutical novelties
Maiorana, A., & Dionisi‐Vici, C. (2017) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-017-0059-x · Cited by 23
“In HI, the major vulnerability of brain in early life is related to the lack of energy substrate for cerebral activity, which is mainly dependent on glucose, accounting for 40–60% of basal metabolic rate (Holliday 1971; Goyal et al 2014).”
BackgroundNon-invasive assessment of neonatal brain oxygen metabolism: A review of newly available techniques
Liu, P., Chalak, L. F., & Lu, H. (2014) · Early Human Development · doi:10.1016/j.earlhumdev.2014.06.009 · Cited by 23
“This rate of increase during early brain development is in line with previous PET literature which showed that cerebral metabolism continues to increase from the third trimester until 4 years old, and then gradually reduces with age afterwards [40,41].”
ResultHow doth the little busy bee: unexpected metabolism
Barros, L. F., Sierralta, J. A., & Weber, B. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.11.005 · Cited by 22
Hagenston, A. M., Bading, H., & Orth, C. B. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a035287 · Cited by 23
“Especially in brain imaging studies, it is typically measured by comparing the rate of brain oxygen consumption (CMRO2) to the rate of brain glucose consumption (CMRgluc) (Goyal et al. 2014; Yellen 2018).”
Chen, Y., Lin, Q., Liao, X., Zhou, C., & Yong He, A. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2013232118 · Cited by 22
“Previous works suggest that AG is critical for task-induced activity (10) and synaptic plasticity (11).”
BackgroundAdiponectin Controls Nutrient Availability in Hypothalamic Astrocytes
Song, N., Jeong, D. Y., Tu, T. H., Park, B. S., Yang, H. R., Kim, Y. J., Kim, J. K., Park, J. T., Yeh, J., Yang, S., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041587 · Cited by 21
Zhang, X., Wu, L., Swerdlow, R. H., & Zhao, L. (2023) · Cells · doi:10.3390/cells12030410 · Cited by 22
“to increased ATP synthesis driven by synaptic activity [41].”
Xu, L., Li, W., Lü, L., Zhang, Z., Cui, Z., Jiang, G., Wang, Y., Meng, Q., Wang, Y.-D., Liu, K., et al. (2023) · Current Microbiology · doi:10.1007/s00284-023-03480-0 · Cited by 23
“PPP non-oxidative branch-derived nucleotide biosynthesis is critical for synapse formation in neurons [44], which affects the development and metabolism of the brain.”
Backgroundβ-amyloid monomers drive up neuronal aerobic glycolysis in response to energy stressors
Santangelo, R., Giuffrida, M. L., Satriano, C., Tomasello, M. F., Zimbone, S., & Copani, A. (2021) · Aging · doi:10.18632/aging.203330 · Cited by 21
“AG has been associated with synaptic activity [4] and is considered an adaptive advantage over OP for those areas requiring a fast ATP supply to active synapses and a fast synaptic turnover [1, 5].”
BackgroundVilleneuve, L. M., Stauch, K. L., & Fox, H. S. (2014) · Journal of Proteomics · doi:10.1016/j.jprot.2014.07.011 · Cited by 20
“Furthermore, aerobic glycolysis in the brain has been shown to correlate with synaptic formation and growth [35].”
BackgroundGene expression associated with individual variability in intrinsic functional connectivity
Li, L., Wei, Y., Zhang, J., Ma, J., Yi, Y., Gu, Y., Li, L. M. W., Lin, Y., & Dai, Z. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.118743 · Cited by 19
Mitochondrial protein synthesis and the bioenergetic cost of neurodevelopment
Bülow, P., Patgiri, A., & Faúndez, V. (2022) · iScience · doi:10.1016/j.isci.2022.104920 · Cited by 18
Synaptic Plasticity and the Warburg Effect
Magistretti, P. J. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.12.012 · Cited by 20
Astroglial signalling in health and disease
Verkhratsky, A., & Zorec, R. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.07.026 · Cited by 22
“Perhaps this reflects the clinically observed hypo-energetic brain states [17, 47], and it was proposed that this may be prevented by augmenting the activity of the noradrenergic system [52, 90].”
Integrating and interpreting brain maps
Hansen, J. Y., & Mišić, B. (2025) · Trends in Neurosciences · doi:10.1016/j.tins.2025.06.003 · Cited by 23
The Unfolded Protein Response: A Double-Edged Sword for Brain Health
Gebert, M., Sławski, J., Kalinowski, L., Collawn, J. F., & Bartoszewski, R. (2023) · Antioxidants · doi:10.3390/antiox12081648 · Cited by 21
Autophagy regulator ATG5 preserves cerebellar function by safeguarding its glycolytic activity
Tutas, J., Tolve, M., Ozer, E., Ickert, L., Klein, I., Silverman, Q., Liebsch, F., Dethloff, F., Giavalisco, P., Endepols, H., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-024-01196-4 · Cited by 20
“…via autophagy in non-neuronal cells 19–21, 50 , while GLUTs are known to be trafficked within the We next hypothesized that autophagy, mediated by ATG5, limits glycolysis by degrading cerebellar GLUT2, a function potentially critical during brain maturation when glycolytic demand decreases 54 .”
Energy metabolism in neuronal/glial induction and in iPSC models of brain disorders
Mlody, B., Lorenz, C., Inak, G., & Prigione, A. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.02.018 · Cited by 20
miR-124 coordinates metabolic regulators acting at early stages of human neurogenesis
Son, G., Na, Y., Kim, Y., Son, J.-H., Clemenson, G. D., Schafer, S. T., Yoo, J.-Y., Parylak, S., Paquola, A. C. M., Do, H., et al. (2024) · Communications Biology · doi:10.1038/s42003-024-07089-2 · Cited by 21
A genetic perspective on glucose consumption in the cerebral cortex during human development
Caravas, J., & Wildman, D. E. (2014) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12333 · Cited by 18
“Thus, one possible explanation for transcriptional neoteny in humans is the observed pattern of increased aerobic glycolysis that occurs during the development of human synapses [7].”
BackgroundInfluentialBenveniste, H., Dienel, G. A., Jacob, Z., Lee, H., Makaryus, R., GJEDDE, A. H., Hyder, F., & Rothman, D. L. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00631 · Cited by 18
“1, inferring enhanced non-oxidative metabolism of glucose during early childhood (Goyal et al., 2014).”
BackgroundMethodInfluentialCryer, P. E., & Arbeláez, A. M. (2016) · Wiley eBooks · doi:10.1002/9781118924853.ch35 · Cited by 19
L-Lactate Administration Improved Synaptic Plasticity and Cognition in Early 3xTg-AD Mice
Wang, Y., Zhao, J., & Zhao, L. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26041486 · Cited by 19
“Furthermore, the metabolic significance of AG extends to neurodevelopmental processes, as evidenced by the colocalization of high AG activity regions with gene expression profiles governing synaptic plasticity, neurite outgrowth, and neural circuit remodeling [4].”
Sulfotransferase 4A1 activity facilitates sulfate-dependent cellular protection to oxidative stress
Brettrager, E. J., Meehan, A. W., Falany, C. N., & van Waardenburg, R. C. A. M. (2022) · Scientific Reports · doi:10.1038/s41598-022-05582-4 · Cited by 17
Aronoff, J. E., Ragin, A. B., Wu, C., Markl, M., Schnell, S., Shaibani, A., Blair, C., & Kuzawa, C. W. (2022) · International Journal of Obesity · doi:10.1038/s41366-022-01065-8 · Cited by 17
“For instance, it has been argued that the childhood peak in CMRO2 could be blunted by as much as 30% compared to CMRglu [26], which, if correct, would obscure the apparent strength of the relationship between brain metabolism and adiposity if changes in cerebral oxygen metabolism are assessed.”
BackgroundLi, Y., Wu, J., Ma, J., Li, S., Xue, X., Dong, W., Shan, C., Hua, X., Zheng, M., & Xu, J. (2022) · Diabetes · doi:10.2337/db21-0600 · Cited by 18
Regional patterns of human cortex development correlate with underlying neurobiologyPreprint
Lotter, L. D., Saberi, A., Hansen, J. Y., Mišić, B., Paquola, C., Barker, G. J., Bokde, A. L. W., Desrivières, S., Flor, H., Grigis, A., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.05.539537 · Cited by 17
Sakimura, K., Kawai, T., Nashida, R., Ishida, Y., Harada, K., Suzuki, T., Okuma, C., & Cole, G. M. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01552-2 · Cited by 18
“AG is a non-oxidative metabolism of glucose despite the presence of abundant oxygen that accounts for 10–12% of glucose used by the adult human brain [14].”
BackgroundLactate and Lactylation in AKI ‐to‐ CKD : Epigenetic Regulation and Therapeutic Opportunities
Hou, Y., Liu, D., Guo, Z., Wei, C., Cao, F., Xu, Y., Feng, Q., & Liu, F. (2025) · Cell Proliferation · doi:10.1111/cpr.70034 · Cited by 18
A primer on copper biology in the brain
Lane, A. R., Roberts, B. R., Fahrni, C. J., & Faúndez, V. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.106974 · Cited by 15
“SLC31A1 (CTR1), followed by a brief summary of the role of copper deficiency in more prevalent diseases such as Parkinson ’ s disease, amyotrophic lateral sclerosis, Alzheimer ’ s disease, and schizophrenia.”
Regional and interindividual relationships between cerebral perfusion and oxygen metabolism
Henriksen, O. M., GJEDDE, A. H., Vang, K., Law, I. G., Aanerud, J., & Rostrup, E. (2021) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00939.2020 · Cited by 16
“, variable efficiency due to uncoupling (13), use of alternate energy substrates such as lactate (42) or ketone bodies (43), presence of aerobic glycolysis (44), or variable capillary density or capillary transit time heterogeneity that both could require higher perfusion to maintain tissue O2 pressure (45).”
BackgroundThe Activation of GPR27 Increases Cytosolic L-Lactate in 3T3 Embryonic Cells and Astrocytes
Dolanc, D., Zorec, T. M., Smole, Z., Maver, A., Horvat, A., Pillaiyar, T., Bobnar, S. T., Vardjan, N., Kreft, M., Chowdhury, H. H., et al. (2022) · Cells · doi:10.3390/cells11061009 · Cited by 20
“In astrocytes, this form of metabolism is operative in some CNS areas [15], as is the metabolic responsiveness to insulin by increasing the levels of glycogen [7].”
BackgroundInfluentialXiong, X., Liang, Y.-J., Zhang, X., Yang, S.-H., Zhong, Z., Liu, S., Sun, J., Tang, Y. M., & Yu, S. (2023) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2206168 · Cited by 16
Evidence for direct CO2 ‐mediated alterations in cerebral oxidative metabolism in humans
Caldwell, H. G., Hoiland, R. L., Bain, A. R., Howe, C. A., Carr, J. M. J. R., Gibbons, T. D., Durrer, C. G., Tymko, M. M., Stacey, B. S., Bailey, D. M., et al. (2024) · Acta Physiologica · doi:10.1111/apha.14197 · Cited by 16
“…removal 81 ; (6) is required for the degradation of glutamate by astrocytes 82 ; or (7) facilitates biosynthetic processes by production of precursor metabolites via the pentose phosphate pathway, 44,83 such as; e.g., cellular proliferation, DNA replication, 84 and fatty acid synthesis.”
A neurometabolic mechanism involving dmPFC/dACC lactate in physical effort-based decision-making
Clairis, N., Barakat, A., Brochard, J., Xin, L., & Sandi, C. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02726-y · Cited by 21
Barger, N., Sheley, M. F., & Schumann, C. M. (2014) · The Journal of Comparative Neurology · doi:10.1002/cne.23707 · Cited by 16
“…dendritic and synaptic morphology (Huttenlocher and Dabholkar, 1997; Petanjek et al., 2011) occur in tandem with the increased rates of aerobic glycolysis (Goyal et al., 2014) that are theorized to provide anabolic support for this active period of cellular development (Bauernfeind et al., 2014).”
BackgroundGoyal, M. S., Gordon, B. A., Couture, L. E., Flores, S. E., Xiong, C., Morris, J. C., Raichle, M. E., Benzinger, T. L. S., & Vlassenko, A. G. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.08.019 · Cited by 16
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“developmentally, and according to neuronal activity (Goyal et al., 2014; Madsen et al., 1995; Settergren et al., 1976; Vaishnavi et al., 2010), and reflects ‘aerobic glycolysis’ and pentose phosphate pathway (PPP) activities.”
InfluentialTaga, G., Watanabe, H., & Homae, F. (2017) · Neurophotonics · doi:10.1117/1.nph.5.1.011017 · Cited by 16
Yang, S., Tang, Y.-Y., Zeng, D., Tian, Q., Wei, H., Wang, C., Zhang, P., Chen, Y., Zou, W., & Tang, X. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113562 · Cited by 15
Kahali, S., Raichle, M. E., & Yablonskiy, D. A. (2021) · Brain Sciences · doi:10.3390/brainsci11121565 · Cited by 16
“Networks at the top of the hierarchy are less myelinated [59], exhibit higher levels of aerobic glycolysis [59,60], and harbor neotenous genes [49].”
BackgroundSelf-citationSystemic proteome phenotypes reveal defective metabolic flexibility in Mecp2 mutants
Zlatic, S. A., Werner, E., Surapaneni, V., Lee, C. E., Gokhale, A., Singleton, K. S., Duong, D. M., Crocker, A. J., Gentile, K. L., Middleton, F. A., et al. (2023) · Human Molecular Genetics · doi:10.1093/hmg/ddad154 · Cited by 15
An Evolutionary Perspective of Dyslexia, Stress, and Brain Network Homeostasis
Kershner, J. R. (2021) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2020.575546 · Cited by 20
Astrocytes in the pathophysiology of neuroinfection
Zorec, R., & Verkhratsky, A. (2022) · Essays in Biochemistry · doi:10.1042/ebc20220082 · Cited by 16
Wang, L., Chaudhari, K., Winters, A., Sun, Y., Liu, R., & Yang, S.-H. (2022) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x221077341 · Cited by 14
Luppi, A. I., Rosas, F. E., Noonan, M. P., Mediano, P. A. M., Kringelbach, M. L., Carhart-Harris, R. L., Stamatakis, E. A., Vernon, A. C., & Turkheimer, F. (2022) · The Neuroscientist · doi:10.1177/10738584221138032 · Cited by 15
Béland-Millar, A., Kirby, A., Truong, Y., Ouellette, J., Yandiev, S., Bouyakdan, K., Pileggi, C. A., Naz, S., Yin, M., Carrier, M., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112485 · Cited by 14
Male increase in brain gene expression variability is linked to genetic risk for schizophrenia
Chen, J., Cao, H., Meyer‐Lindenberg, A., & Schwarz, E. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0200-0 · Cited by 13
Metabolic changes in human brain evolution
Bauernfeind, A. L., & Babbitt, C. C. (2020) · Evolutionary Anthropology Issues News and Reviews · doi:10.1002/evan.21831 · Cited by 13
“If so, what is so energetically costly about the developing brain? In addition to being used as a source of fuel, glucose can also be processed through various anaerobic pathways to create biomolecules that are essential for the growth and maturation of neurons [35, 36, 40, 41].”
BackgroundBoley, N., Patil, S., Garnett, E. O., Li, H., Chugani, D. C., Chang, S., & Chow, H. M. (2021) · Journal of Speech Language and Hearing Research · doi:10.1044/2020_jslhr-20-00325 · Cited by 13
“exacerbated in brain regions with relatively high energy utilization, especially during preschool age, a period of sharp increases in brain metabolism (Chugani et al., 1987; Goyal et al., 2014).”
BackgroundJia, J., Tao, W., Chen, T., Zhong, Q., Sun, J., Xu, Y., Sui, X., Chen, C., & Zhang, Z. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03585-4 · Cited by 13
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“Thus, astrocytic lactate generated through aerobic glycolysis was shown to be essential for brain development, supporting the biosynthetic requirements of synaptic growth and remodeling [44].”
BackgroundNeuronal aerobic glycolysis exacerbates synapse loss in aging mice
Zhou, W., Yang, X., Wang, H., Yao, W., Chu, D., & Wu, F. (2023) · Experimental Neurology · doi:10.1016/j.expneurol.2023.114590 · Cited by 13
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Heritability of cortical morphology reflects a sensory-fugal plasticity gradientPreprint
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Brain structure in autoimmune Addison’s disease
Westeinde, A. V., Padilla, N., Sanchez, M. S., Fletcher‐Sandersjöö, S., Kämpe, O., Bensing, S., & Lajić, S. (2022) · Cerebral Cortex · doi:10.1093/cercor/bhac389 · Cited by 11
“2015), and the high energetic demand of these parietal nodes might make them more vulnerable (Goyal et al. 2014).”
BackgroundThe interplay between glucose and ketone bodies in neural stem cell metabolism
Molloy, J. W., & Barry, D. (2024) · Journal of Neuroscience Research · doi:10.1002/jnr.25342 · Cited by 11
“Developing brain regions displaying increased levels of aerobic glycolysis also showed increased expression levels of genes responsible for synapse formation and growth (Goyal et al., 2014).”
BackgroundUnleashing metabolic power for axonal regeneration
Yang, X.-Y., & Zhou, B. (2024) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2024.07.001 · Cited by 12
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The Effect of High-Altitude Hypoxia on Neuropsychiatric Functions
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“…total body weight, it requires a substantial amount of energy, * 20%, owing to its extensive neural network comprising around 100 billion neurons, a comparable number of glial cells (von Bartheld et al., 2016), and trillions of intricate synapses (Goyal et al., 2014; Magistretti and Allaman, 2015).”
Increased White Matter Aerobic Glycolysis in Multiple Sclerosis
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“The AG accounts for (cid:1) 10% of glucose utilization in healthy young brains, 21 declines with age, 22 – 24 relates to synaptic plasticity, 25 and is decreased in degenerative diseases.”
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Analysis of Presenilin 1 and 2 interacting proteins in mouse cerebral cortex during development
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“On the other hand, knockout of PS2 survived well without any defect in the brain morphology (Herreman et al., 1999), indicating that the protease might not contribute to brain developmental processes directly and may serve to compensate PS1 functions postnatally (Wang et al., 2003).”
BackgroundPersistent changes in extracellular lactate dynamics following synaptic potentiation
Bingul, D., Kalra, K., Murata, E. M., Belser, A., & Dash, M. B. (2020) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2020.107314 · Cited by 13
“Consistent with these observations, the rate of aerobic glycolysis during development is highest during periods of robust synaptic growth and is correlated in adulthood with the expression of genes responsible for synapse formation and growth (Goyal et al., 2014).”
BackgroundInfluentialTalbot, J. S., Perkins, D. R., Tallon, C. M., Dawkins, T. G., Douglas, A. J. M., Beckerleg, R., Crofts, A., Wright, M. E., Davies, S., Steventon, J. J., et al. (2023) · Experimental Physiology · doi:10.1113/ep091279 · Cited by 10
“, 2017), with metabolic demand and gCBF highest during mid-childhood (Goyal et al., 2014; Paniukov et al., 2020), before declining in a brain region-specific manner during adolescence (Giedd et al.”
BackgroundLocus Coeruleus Noradrenergic Neurons and Astroglia in Health and Disease
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Conservative and disruptive modes of adolescent change in brain functional connectivityPreprint
Váša, F., Romero-García, R., Kitzbichler, M. G., Seidlitz, J., Whitaker, K. J., Vaghi, M. M. S., Kundu, P., Patel, A. X., Fonagy, P., Dolan, R. J., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/604843 · Cited by 9
“, 2014), while primary sensory and motor regions progressively reduce glucose metabolism by AG (and increase oxidative metabolism) from early childhood into adolescence (Vaishnavi et al., 2010; Goyal et al., 2014).”
BackgroundMethodInfluentialPourmajidian, M., Hansen, J. Y., Shafiei, G., Mišić, B., & Dagher, A. (2026) · PLoS Biology · doi:10.1371/journal.pbio.3003619 · Cited by 11
“Aerobic glycolysis is considered a measure of non-oxidative glucose metabolism in the presence of oxygen [28,60,136,137], important for tissue biosynthesis [74,138,139].”
InfluentialMR Imaging Differences in the Circle of Willis between Healthy Children and Adults
Guilliams, K. P., Gupta, N., Srinivasan, S., Binkley, M. M., Ying, C., Couture, L. E., Gross, J., Wallace, A. N., McKinstry, R. C., Vo, K. D., et al. (2021) · American Journal of Neuroradiology · doi:10.3174/ajnr.a7290 · Cited by 9
Self-citationHoránszky, A., Shashikadze, B., Elkhateib, R., Lombardo, S. D., Lamberto, F., Zana, M., Menche, J., Fröhlich, T., & Dinnyés, A. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1236243 · Cited by 8
Franco, R., Serrano‐Marín, J., Navarro, G., & Rivas‐Santisteban, R. (2023) · Antioxidants · doi:10.3390/antiox12101869 · Cited by 8
“In fact, although it makes up a small percentage of the total body weight, oxygen consumption of the brain is estimated to be >20% of the human body’s requirements, with surges of up to 40% [46–48].”
BackgroundYang, Y. Q., Zhou, D., Min, S., Liu, D., Zou, M., Yu, C., Chen, L., Huang, J., & Hong, R. (2024) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2024.173775 · Cited by 8
“(Goyal et al., 2014).”
Ismaili, A. R. A., Vestergaard, M. B., Hansen, A. E., Larsson, H. B. W., Johannesen, H. H., Law, I. G., & Henriksen, O. M. (2018) · PLoS ONE · doi:10.1371/journal.pone.0197807 · Cited by 8
“The lower gCBF values found in aged subjects compared to younger subjects is thus in agreement with previous publications applying PCM and probably reflects mainly a true age related gCBF decline also reported using a range other techniques [12, 25, 26] and in lesser degree methodological bias.”
BackgroundResultBayliak, M. M., Mosiichuk, N. M., Sorochynska, O. M., Kuzniak, O. V., Sishchuk, L. O., Hrushchenko, A. O., Semchuk, A. O., Pryimak, T. V., Vasylyk, Y. V., Gospodaryov, D. V., et al. (2021) · Biogerontology · doi:10.1007/s10522-021-09918-x · Cited by 8
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Synaptic signaling modeled by functional connectivity predicts metabolic demands of the human brain
Klug, S., Murgaš, M., Godbersen, G. M., Hacker, M., Lanzenberger, R. R., & Hahn, A. (2024) · NeuroImage · doi:10.1016/j.neuroimage.2024.120658 · Cited by 8
“The interpretation that FC input relates to synaptic signaling is also supported by imaging transcriptomics (Diez and Sepulcre, 2018; Martins et al., 2021), where genes primarily involved in synaptic signaling were related to the explained CMRGlu (Chen et al., 2021; Goyal et al., 2014).”
BackgroundMethodPrenatal social disadvantage is associated with alterations in functional networks at birth
Nielsen, A. N., Triplett, R. L., Bernardez, L. M., Tooley, U. A., Herzberg, M. P., Lean, R. E., Kaplan, S., Meyer, D., Kenley, J. K., Alexopoulos, D., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2405448121 · Cited by 10
“Because metabolic rates vary across the brain [e.g., increased aerobic glycolysis in the default mode network (DMN)] ( 39 ), stress hormone - induced changes in energy demand ( 40 ) may contribute to patterns of intrinsic activity that differ by functional network.”
Self-citationHor, K., Dearden, L., Herzstein, E., Ozanne, S. E., Hardingham, G. E., & Drake, A. J. (2025) · Journal of Neuroendocrinology · doi:10.1111/jne.70046 · Cited by 7
“25,73 The sex difference in the risk of postnatal hypoglycemia appears to recapitulate observations in humans where male infants of mothers with Type 1 or gestational diabetes have a higher risk of neonatal hypoglycemia.”
Cortical hierarchy underlying homeostatic sleep pressure alleviation
Zou, Q., Zou, G., Wang, S., Wang, Y., Xu, J., Long, Y., Zhou, S., Wu, X., Yang, G., Qin, L., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-64989-5 · Cited by 10
“Indeed, brain regions with the highest glycolysis exhibit increased gene expression related to synapse formation and growth 78 , which is tightly correlated with the function of sleep 7,8 .”
Scale-spanning crosstalk between metabolism and information processing
Barros, L. F., Fernández‐Moncada, I., Marsicano, G., Ruminot, I., Saab, A. S., & Weber, B. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.10.012 · Cited by 8
Inverse correlation between Alzheimer’s disease and cancer from the perspective of hypoxia
Su, Z., Zhang, G., Li, X., & Zhang, H. (2023) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2023.07.002 · Cited by 7
“of glycolysis, are also the most sensitive to AD, proving that these regions are more susceptible to energy depletion (Goyal et al., 2014).”
Zhang, X., Gao, R., Yang, L., Zhu, Y., Zhang, T., Shen, X., Gu, W., Yang, L., & Peng, S. (2024) · Clinical and Translational Discovery · doi:10.1002/ctd2.287 · Cited by 8
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Early life adversity jointly regulates body-mass index and working memory development
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A suite of neurophotonic tools to underpin the contribution of internal brain states in fMRI
Mächler, P., Broggini, T., Matéo, C., Thunemann, M., Fomin-Thunemann, N., Doran, P. R., Şencan, İ., Kılıç, K., Desjardins, M., Uhlířová, H., et al. (2021) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2021.100273 · Cited by 6
NIX‐ing mitochondria: from development to pathology
Deczkowska, A., & Schwartz, M. (2017) · The EMBO Journal · doi:10.15252/embj.201797110 · Cited by 7
“…during development also rely on autophagy signaling (Va´zquez et al , 2012; Petri et al , 2017), and aerobic glycolysis (glycolysis in presence of oxygen) was proposed to occur in the human neonatal brain specifically in regions where synaptic growth rates are the highest (Goyal et al , 2014).”
Theriault (n.d.) · doi:10.31234/osf.io/pkzr8 · Cited by 51
The role of immune cells glycolysis in neuroinflammation secondary to intracerebral hemorrhage
Luo, B., Liu, S., Zheng, L., Zhang, B., Shang, Y., Shang, T., Zheng, J., Kuang, B., & Zou, W. (2025) · Clinical Immunology · doi:10.1016/j.clim.2025.110543 · Cited by 7
Adaptive protein synthesis in genetic models of copper deficiency and childhood neurodegeneration
Lane, A. R., Scher, N. E., Bhattacharjee, S., Zlatic, S. A., Roberts, A. M., Gokhale, A., Singleton, K. S., Duong, D. M., McKenna, M., Liu, W. L., et al. (2025) · Molecular Biology of the Cell · doi:10.1091/mbc.e24-11-0512 · Cited by 6
Neuroenergetics and “General Intelligence”: A Systems Biology Perspective
Debatin, T. (2020) · Journal of Intelligence · doi:10.3390/jintelligence8030031 · Cited by 6
“However, during development, glycolysis accounts for up to 30% of brain metabolism, and in some brain areas, it still accounts for up to 25% of glucose utilization in adults even in the “resting” brain (Goyal et al. 2014; Magistretti and Allaman 2015).”
BackgroundEdited magnetic resonance spectroscopy in the neonatal brain
Song, Y., Lally, P., Lopez, M. Y., Oeltzschner, G., Nebel, M. B., Gagoski, B. A., Kecskemeti, S., Hui, S. C. N., Zöllner, H. J., Shukla, D., et al. (2021) · Neuroradiology · doi:10.1007/s00234-021-02821-9 · Cited by 6
“It also acts as a signaling molecule, which is necessary for memory consolidation in learning tasks in animals [82–84], regulation in the GABAergic system [85], neuronal plasticity [86, 87], and neuronal excitability [88].”
BackgroundVLSM-Net: A Fusion Architecture for CT Image Segmentation
Gao, Y.-C., Guo, J. Q., Fu, C., et al. (2023) · Applied Sciences · doi:10.3390/app13074384 · Cited by 6
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“According to literature, the brain metabolic demand (energy use) peaks during childhood [1].”
BackgroundInfluentialZink, A., Priller, J., & Prigione, A. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.02.005 · Cited by 6
“These requirements are even higher during development, as the brains of infants utilize more than 40% of the basal metabolic rate (Goyal et al., 2014).”
BackgroundSpecies-specific mitochondria dynamics and metabolism regulate the timing of neuronal developmentPreprint
Iwata, R., Casimir, P., Erkol, E., Boubakar, L., Planque, M., Ditkowska, M., Vints, K., Poovathingal, S. K., Gaspariunaite, V., Bird, M., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.12.27.474246 · Cited by 6
Hexokinase and Glycolysis: Between Brain Cells Life and Death
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Glutamatergic argonaute2 promotes the formation of the neurovascular unit in mice
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Metadata
- Authors
- Goyal, M. S., Hawrylycz, M., Miller, J. A., Snyder, A. Z., & Raichle, M. E.
- Affiliations
- Washington University in St. Louis (US)
- Allen Institute for Brain Science (US)
- Corresponding author
- Goyal, Manu S.
- Raichle, Marcus E.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 19
- Issue
- 1
- Pages
- 49-57
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4389678
- OpenAlex
- W1974124405
- Cited by
- 459
- References
- 68
- Citations by year
- 2026: 39 · 2025: 38 · 2024: 40 · 2023: 42 · 2022: 39 · 2021: 52 · 2020: 36 · 2019: 32 · 2018: 48 · 2017: 29 · 2016: 16 · 2015: 19 · 2014: 29
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (P01NS080675, P30NS048056, P50NS006833)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- aerobic glycolysis, human brain, brain glucose metabolism, glucose oxidation, synaptic development, synaptogenesis, neoteny, developmental gene expression, child neurodevelopment, mitochondria, synaptic transmission
- MeSH terms
- Adult, Aerobiosis, Brain, Glucose, Glycolysis, Humans, Oxygen Consumption, Synapses, Transcription, Genetic, Gene Expression Regulation, Developmental, Gene Expression Profiling, Gene Ontology
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