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
29 Own result · 11 Own interpretation · 7 Partly supported · 7 Own method · 5 No full text of the sources · 5 No basis given · 3 Supported · 3 Couldn’t confirm · 1 Sources not found · 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)
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.
- 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)
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.
- 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)
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.
Every 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)
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.
- 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)
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.
- 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)
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.
The 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)
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In 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
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.
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
“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
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.
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
“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
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.
- 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)
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.
- 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
hedgedconditional- Asserted: fails — The authors may not 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. 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.
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.
- 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)
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.
- 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)
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.
- 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)
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.
- 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
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.
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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
plaincorrelationaln = 900- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
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
“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
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: fails — The paper may give no reason why it holds.
Probably 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
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.
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
plaindirectSingle case- 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
“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
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.
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
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: 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.
- 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
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.
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
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: 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
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.
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
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.
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
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.
Probably 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
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
“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.
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.
- 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.
A note, not an issue: for example, a cited work that was retracted only after this paper was published, which its authors could not have known.
In the paper
“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).”
Cited work 10.1038/nature07767 · retracted 2023-12-18 · notice 10.1038/s41586-023-06943-3 · this paper published 2014-01
Citations
Cites
1 retracted
RETRACTED ARTICLE: APP binds DR6 to trigger axon pruning and neuron death via distinct caspases
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“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
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“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).”
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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
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An anatomically comprehensive atlas of the adult human brain transcriptome
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“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
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Cited by
Sorted by citations
The brain's default mode network
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Lactate in the brain: from metabolic end-product to signalling molecule
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A Cellular Perspective on Brain Energy Metabolism and Functional Imaging
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“…dorsolateral prefrontal cortex, the superior andmedial frontal gyrus, or the precuneus and posterior cingulate cortex, where it accounts for up to 25% of glucose utilization, whereas in other areas, such as the cerebellum, it is virtually nonexistent (Bauernfeind et al., 2014; Goyal et al., 2014).”
Background13 reasons why the brain is susceptible to oxidative stress
Cobley, J. N., Fiorello, M. L., & Bailey, D. M. (2018) · Redox Biology · doi:10.1016/j.redox.2018.01.008 · Cited by 1,215
Brain Glucose Metabolism: Integration of Energetics with Function
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“An alternative approach is to use the MNI (or voxel) coordinates of each sample (Goyal et al., 2014; Cioli et al., 2014; French and Paus, 2015; Richiardi et al., 2015; Komorowski et al., 2016; Krienen et al., 2016; Rizzo et al., 2016; Burt et al., 2018; Parkes et al., 2017; Romme et al., 2017; Shin…”
BackgroundMethodMetabolic costs and evolutionary implications of human brain development
Kuzawa, C. W., Chugani, H. T., Grossman, L. I., Lipovich, L., Muzik, O., Hof, P. R., Wildman, D. E., Sherwood, C. C., Leonard, W. R., & Lange, N. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1323099111 · Cited by 585
“These ratios do not indicate the percent of RMR or DER used by the brain because some brain glucose uptake (the numerator) is not used in energy production (28).”
BackgroundThe Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor
Valvona, C. J., Fillmore, H. L., Nunn, P. B., & Pilkington, G. J. (2015) · Brain Pathology · doi:10.1111/bpa.12299 · Cited by 570
“Recent studies have shown that the regions of the brain with the highest level of aerobic glycolysis also express increased levels of genes relating to synapse formation and growth, suggesting aerobic glycolysis could be used in brain development to support the biosynthesis required for growth, similarly to cancer cel…”
BackgroundAstrocyte-neuron metabolic cooperation shapes brain activity
Bonvento, G., & Bolaños, J. P. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.07.006 · Cited by 580
The restless brain: How intrinsic activity organizes brain function
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“Overlooked by most neuroscientists is one of the important functions performed by glycolysis which is to provide substrate for biosynthesis [21,103,122].”
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“Changes in brain energetics, neuronal phosphate, and ATP metabolism occur with age (Forester et al., 2010), and elderly individuals have virtually absent global neuronal aerobic glycolysis (Goyal et al., 2014), which creates a pseudohypoxic state.”
A Synergistic Core for Human Brain Evolution and Cognition
Luppi, A. I., Mediano, P. A. M., Rosas, F. E., Holland, N., Fryer, T. D., O’Brien, J. T., Rowe, J. B., Menon, D. K., Bor, D., & Stamatakis, E. A. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01070-0 · Cited by 314
Loss of Brain Aerobic Glycolysis in Normal Human Aging
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Self-citationLactic Acid: No Longer an Inert and End-Product of Glycolysis
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“In the brain, glycolysis is prominent, accounting for 10 –12% of glucose consumption (56).”
BackgroundMitochondria metabolism sets the species-specific tempo of neuronal development
Iwata, R., Casimir, P., Erkol, E., Boubakar, L., Planque, M., Gallego López, I. M., Ditkowska, M., Gaspariunaite, V., Beckers, S., Remans, D., et al. (2023) · Science · doi:10.1126/science.abn4705 · Cited by 312
“Differences in species-specificmetabolic properties of cortical neurons may influence human brain neoteny, which is consistent with previous reports of years-long periods of aerobic glycolysis in the developing human cortex (41).”
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“The brain is the central organ in living organisms and is a major consumer of oxygen to provide uninterrupted supply of energy to approximately 86 billion neurons for their daily activities, it has been estimated it uses almost 20% of the basal oxygen (O2) from the total oxygen supplied to the human body [91,92].”
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“All brain regions utilize a mixture of aerobic glycolysis and oxidative phosphorylation, but the highest resting rates of aerobic glycolysis occur in the DLPFC and VLPFC, while the amygdala and hippocampus have relatively low resting rates (Goyal et al., 2014; Vaishnavi et al., 2010).”
BackgroundGlucose, lactate, and shuttling of metabolites in vertebrate retinas
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“3) Aerobic glycolysis accounts for 2–25% of Glc metabolism in brain (Goyal et al., 2014), but it accounts for 80–96% of glucose consumption in retina (Winkler 1981; Ames et al.”
BackgroundMetabolic reprogramming during neuronal differentiation
Agostini, M., Romeo, F., Inoue, S., Niklison-Chirou, M. V., Elia, A., Dinsdale, D. D., Morone, N., Knight, R. A., Mak, T. W., & Melino, G. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.36 · Cited by 273
“This biosynthetic role is reminiscent of the Warburg effect observed in cancer cells and it has also been recently postulated in the rapidly growing human child brain.(53) Moreover, ATP levels are reduced after 2-DG treatment, suggesting that glycolysis may be a major source of ATP early in the differentiation process…”
BackgroundPleiotropic Mitochondria: The Influence of Mitochondria on Neuronal Development and Disease
Rangaraju, V., Lewis, T. L., Hirabayashi, Y., Bergami, M., Motori, E., Cartoni, R., Kwon, S., & Courchet, J. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.1157-19.2019 · Cited by 264
“, 1981; Attwell and Laughlin, 2001), with even higher metabolic requirements during development (Goyal et al., 2014; Kuzawa et al., 2014).”
BackgroundImpact of puberty on the evolution of cerebral perfusion during adolescence
Satterthwaite, T. D., Shinohara, R. T., Wolf, D. H., Hopson, R. D., Elliott, M. A., Vandekar, S., Ruparel, K., Calkins, M. E., Roalf, D. R., Gennatas, E. D., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1400178111 · Cited by 236
“CBF decline in childhood and adolescence has previously been found to be tightly linked to the decline of glucose metabolism (62).”
BackgroundA transcriptional signature of hub connectivity in the mouse connectome
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“Although many aspects of gene expression in the brain show a developmentally persistent profile (35), it is unclear whether the same transcriptional signature of hub connectivity would be apparent throughout development.”
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“In particular, a recent meta-analysis by Goyal et al. (2014) showed that aerobic glycolysis is greatly increased during childhood, and that regional increases in glycolysis are associated with expression of genes related to synaptic development.”
Persistent metabolic youth in the aging female brain
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“Our recent multitracer PET brain imaging data demonstrate that as the brain ages, its resting metabolism gradually shifts away from a mixture of nonoxidative and oxidative use of glucose to predominantly oxidative metabolism (4, 5).”
BackgroundSelf-citationCultivating Healthy Growth and Nutrition through the Gut Microbiota
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“Approximately 30% of the glucose consumed by the infant brain is accounted for by aerobic glycolysis (versus 12% in adults) (Goyal et al., 2014).”
Brain Fuel Utilization in the Developing Brain
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Glutamate synthesis has to be matched by its degradation – where do all the carbons go?
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BackgroundSynapses: The Brain’s Energy-Demanding Sites
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“Developmentally, these high glycolytic rates correlate with the highest rates of synaptogenesis and axonal and synaptic growth [77], suggesting that, besides supporting energetic demands, glycolysis is also important to support synaptic growth and formation through biosynthetic pathways [55,77].”
BackgroundImaging Adenosine Triphosphate (ATP)
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“2C) with 9 independently produced maps of a range of brain functional and developmental parameters, including 1) evolutionary and postnatal surface expansion of the cortex (27); 2) metabolic rates of glucose, oxygen, and aerobic glycolysis (AG) measured by positron emission tomography (PET) (28); 3) microarray measure…”
Glycolytic Metabolism, Brain Resilience, and Alzheimer’s Disease
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“However, retina and brain have different functions and structures that influence the nature of the interactions between their neurons and glia: i) Aerobic glycolysis accounts for 2–25% of Glc metabolism in brain (3), but it accounts for 80–96% of it in retina (4–6).”
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“In addition, it is interesting that the relatively large glycolytic capacity of brain tissue is most likely attributed to astrocytes [40, 41], and increasing evidence shows that the astrocyte-neuron lactate shuttle is the main way by which lactate transfers to neurons to meet the neuronal energy…”
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“Variation in glucose uptake and metabolism in the brain (9, 12) could have a variety of functional outcomes.”
BackgroundInfluentialGenetic and phylogenetic uncoupling of structure and function in human transmodal cortex
Valk, S. L., Xu, T., Paquola, C., Park, B., Bethlehem, R. A. I., de Wael, R. V., Royer, J., Masouleh, S. K., Bayrak, Ş., Kochunov, P., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29886-1 · Cited by 121
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Hierarchical functional system development supports executive function
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“This suggests that neoteny is inherent in the development of human brain regions with high energy demands that are required for cognitive and memory-related functions (24, 52).”
BackgroundAerobic glycolysis and tau deposition in preclinical Alzheimer's disease
Vlassenko, A. G., Gordon, B. A., Goyal, M. S., Su, Y., Blazey, T. M., Durbin, T. J., Couture, L. E., Christensen, J. J., Jafri, H., Morris, J. C., et al. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.03.014 · Cited by 107
Self-citationMetabolic changes favor the activity and heterogeneity of reactive astrocytes
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“The astrocytes’ glycolytic capacity is important for brain tissues [27,28] because the increased glycolysis in astrocytes is critical not only for their survival during hypoxia [34] but also in the regulation of brain diseases.”
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“CRP was used as the main marker of a peripheral inflammation, consistent with other studies in MDD (Howren et al., 2009; Haapakoski et al., 2015).”
ResultImaging transcriptomics of brain disorders
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“While many genes show neotenous patterns of expression (30), many others show marked changes in transcriptional”
BackgroundEarly remodeling of the neocortex upon episodic memory encoding
Bero, A. W., Meng, J., Cho, S., Shen, A. H., Canter, R. G., Ericsson, M., & Tsai, L. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1408378111 · Cited by 116
“Indeed, elevated aerobic glycolysis in the mPFC is closely associated with enhanced expression of genes related to synaptic remodeling and memory formation (45).”
BackgroundGSEA of mouse and human mitochondriomes reveals fatty acid oxidation in astrocytes
Eraso‐Pichot, A., Brasó‐Vives, M., Golbano, A., Menacho, C., Claro, E., Galea, E., & Masgrau, R. (2018) · Glia · doi:10.1002/glia.23330 · Cited by 105
“Interestingly, a meta-analysis of glucose and oxygen consumption across the human lifespan concluded that anaerobic glycolysis appears to decrease dramatically in the elderly, whereas oxygen consumption is slightly higher (Goyal et al., 2014).”
BackgroundBrain energy metabolism: A roadmap for future research
Rae, C. D., Baur, J. A., Borges, K., Dienel, G. A., Díaz‐García, C. M., Douglass, S. R., Drew, K. L., Duarte, J. M. N., Durán, J., Kann, O., et al. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16032 · Cited by 113
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Cerebral Lactate Metabolism After Traumatic Brain Injury
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Focusing on mitochondria in the brain: from biology to therapeutics
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“Throughout human lifespan, the brain glucose utilization peaks at age 4–5 years dominantly in the form of aerobic glycolysis [45].”
BackgroundAgeing and inflammation – A central role for mitochondria in brain health and disease
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Brain aerobic glycolysis functions and Alzheimer’s disease
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“[81] 32 Clin Transl Imaging (2015) 3:27–37”
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“Remarkably, these regions correspond to brain areas where the expression of genes related to synapse formation and growth, which is high during the childhood, persists in adults (Goyal et al., 2014).”
BackgroundDebates on the dorsomedial prefrontal/dorsal anterior cingulate cortex: insights for future research
Clairis, N., & Lopez‐Persem, A. (2023) · Brain · doi:10.1093/brain/awad263 · Cited by 111
Metabolic Plasticity of Astrocytes and Aging of the Brain
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“The relatively large glycolytic capacity of brain tissue is most likely attributed to astrocytes [1,10], where glycolysis appears to have a larger enzymatic capacity than oxidative metabolism [11], and neuronal glycolysis is limited [12].”
BackgroundLactate topography of the human brain using hyperpolarized 13C-MRI
Lee, C. Y., Soliman, H., Geraghty, B. J., Chen, A. P., Connelly, K. A., Endre, R., Perks, W. J., Heyn, C., Black, S. E., & Cunningham, C. H. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.116202 · Cited by 88
Can the emerging field of immunometabolism provide insights into neuroinflammation?
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“Indeed, aerobic glycolysis has been found to account for 10% of the glucose consumed by the adult human brain (Goyal et al., 2014).”
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NH4+ triggers the release of astrocytic lactate via mitochondrial pyruvate shunting
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The Neuroscience of Adolescence
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Enhancement of Astroglial Aerobic Glycolysis by Extracellular Lactate-Mediated Increase in cAMP
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“Stimulation Increases [lactate]i in Astrocytes Genes associated with aerobic glycolysis are mainly expressed in neocortical areas where neuronal cell plasticity is taking place (Goyal et al., 2014).”
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“, neotony) that is related to synapse formation and growth (20).”
BackgroundInfluentialSelf-citationAggression is associated with aerobic glycolysis in the honey bee brain1
Chandrasekaran, S., Rittschof, C. C., Djukovic, D., Gu, H., Raftery, D., Price, N. D., & Robinson, G. E. (2015) · Genes Brain & Behavior · doi:10.1111/gbb.12201 · Cited by 83
“Given the high energetic demands for neural function, it is surprising to see this less efficient metabolic state (Goyal et al. 2014).”
BackgroundInfluentialMetabolic regulation of neurodifferentiation in the adult brain
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Glial glucose fuels the neuronal pentose phosphate pathway for long-term memory
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“Later, Goyal et al. 15 used nonlinear dimension reduction across whole-genome spatial expression, again from only one of the six AHBA brains, to show that aerobic glycolysis was associated with a second transcriptional component.”
BackgroundThe Effects of Early-Life Iron Deficiency on Brain Energy Metabolism
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Energy metabolism in childhood neurodevelopmental disorders
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Sodium signaling and astrocyte energy metabolism
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“Goyal et al. (2014) recently demonstrated that periods and regions of the brain where aerobic glycolysis is most active correspond to a high expression of plasticity genes in particular those associated with synaptic remodeling.”
BackgroundInfluentialAerobic Glycolysis in the Brain: Warburg and Crabtree Contra Pasteur
Barros, L. F., Ruminot, I., Martín, A. S., Lerchundi, R., Fernández‐Moncada, I., & Baeza‐Lehnert, F. (2020) · Neurochemical Research · doi:10.1007/s11064-020-02964-w · Cited by 77
Brain aerobic glycolysis and resilience in Alzheimer disease
Goyal, M. S., Blazey, T., Metcalf, N. V., McAvoy, M. P., Strain, J. F., Rahmani, M., Durbin, T. J., Xiong, C., Benzinger, T. L. S., Morris, J. C., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2212256120 · Cited by 75
“…here, accounting for prior studies that demonstrate that whole brain glycolysis quantitatively decreases with age and in Alzheimer’s disease (14–15 Increased age was associated with decreases in GI in the superior frontal, superior parietal, caudal middle frontal, medial orbitofrontal, and…”
Self-citationEnergy metabolic pathways in neuronal development and function
Rumpf, S., Sanal, N., & Marzano, M. (2023) · Oxford Open Neuroscience · doi:10.1093/oons/kvad004 · Cited by 77
“In fact, a meta-analysis of gene expression and energy consumption shows a strong correlation between aerobic glycolysis and neuronal development [26].”
BackgroundWang, Y., Li, P., Xu, Y., Feng, L., Fang, Y., Song, G., Li, X., Zhu, Z., Wang, W., Mei, Q., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03303-4 · Cited by 77
“…aerobic glycolysis is observed during early development with the highest synaptic growth rates, while in adults, relatively higher aerobic glycolysis is found in neotenous regions, and during aging, aerobic glycolysis is downregulated, accompanied by decreased plasticity in the brain [81, 82].”
Cioli, C., Abdi, H., Beaton, D., Burnod, Y., & Mesmoudi, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115913 · Cited by 69
“, in [1–3]) with the topographic organization of gene expressions [4–6].”
BackgroundThe pyruvate dehydrogenase complex: Life’s essential, vulnerable and druggable energy homeostat
Stacpoole, P. W., & McCall, C. E. (2023) · Mitochondrion · doi:10.1016/j.mito.2023.02.007 · Cited by 70
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Dependence of hippocampal function on ERRγ-regulated mitochondrial metabolism
Pei, L., Mu, Y., Leblanc, M., Alaynick, W., Barish, G. D., Pankratz, M., Tseng, T. W., Kaufman, S., Liddle, C., Yu, R. T., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.03.004 · Cited by 65
“This is significant because different brain cell types (neurons, astrocytes, oligodendrocytes, etc.) and same cell types in different brain regions and during different developmental stages exhibit diverse metabolic properties (Fünfschilling et al., 2012; Goyal et al., 2014; Vilchez et al., 2007).”
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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