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Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism
Open accessAbstract
SUMMARY Oligodendrocytes make myelin and support axons metabolically with lactate. However, it is unknown how glucose utilization and glycolysis are adapted to the different axonal energy demands. Spiking axons release glutamate and oligodendrocytes express NMDA receptors of unknown function. Here we show that the stimulation of oligodendroglial NMDA receptors mobilizes glucose transporter GLUT1, leading to its incorporation into the myelin compartment in vivo. When myelinated optic nerves from conditional NMDA receptor mutants are challenged with transient oxygen-glucose deprivation, they show a reduced functional recovery when returned to oxygen-glucose but are indistinguishable from wild-type when provided with oxygen-lactate. Moreover, the functional integrity of isolated optic nerves, which are electrically silent, is extended by preincubation with NMDA, mimicking axonal activity, and shortened by NMDA receptor blockers. This reveals a novel aspect of neuronal energy metabolism in which activity-dependent glutamate release enhances oligodendroglial glucose uptake and glycolytic support of fast spiking axons.
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TL;DR
Oligodendroglial NMDA receptor activation mobilizes GLUT1 to the cell surface/myelin and increases glucose import and lactate release, coupling axonal spiking to oligodendroglial glycolytic support. Conditional NR1 loss reduces myelin GLUT1, impairs recovery from oxygen-glucose deprivation unless lactate is supplied, and causes late axonal and neurological deficits.
Key findings
- In cultured oligodendrocytes, NMDA triggered GLUT1 surface redistribution within 30 min, blocked by D-AP5; biotinylation showed a 2-fold surface GLUT1 increase, FRET glucose sensor measurements rose from 0.56 ± 0.04 mM at baseline to 1.85 ± 0.24 mM after NMDA, and NMR showed a 24% ± 4% increase in U-13C-lactate release; MCT1 was unchanged.
- In Grin1flox/flox*Cnp1Cre/+ (NR1 cKO) optic nerves, myelin GLUT1 was reduced by 80%, recombination reached 62% ± 8% at P96, and myelin was transiently thinner at P18–P20 but normal at P70.
- After 60-min oxygen-glucose deprivation, NR1 mutant optic nerves recovered 50% less than controls; lactate reperfusion restored recovery equal to or better than glucose; wild-type nerves preincubated 16 hr with NMDA/Gly maintained high-frequency conduction better, while D-AP5/7CKA worsened it, and without NMDA, 25 Hz stimulation caused about 10% decline per min.
- Adult NR1 mutants showed faster high-frequency spinal CAP amplitude drop and slower recovery, a 1-year rotarod deficit, and at 19 months a severe neurological phenotype including hind limb clasping, hunchback, and ataxia with neuroinflammation and axonopathy in white matter tracts.
Methods
- Conditional NR1 knockout mice (Grin1flox/flox*Cnp1Cre/+) versus controls, plus primary mouse/rat OPC cultures and immunopanned oligodendrocytes; assays included immunocytochemistry, surface biotinylation, FRET glucose sensor imaging, 2-deoxyglucose uptake, NMR lactate release, myelin purification/immunoblot, immunogold EM, optic nerve CAP recordings with OGD and graded frequency, in vivo spinal cord CAP recordings, rotarod, and clinical scoring.
- Statistics used Mann-Whitney, two-tailed Student’s t tests, one-way or two-way ANOVA with Bonferroni post-test, or linear mixed effects models; significance was set at *p < 0.05, p < 0.01, *p < 0.001, with data as means ± SEM.
Limitations
- Stated: astrocytes may compensate some metabolic functions in oligodendroglial NMDA receptor mutants; acute ex vivo NMDA receptor blockade did not visibly reduce recovery from OGD, which the authors attribute to different timescales between development and pharmacology; some mechanistic data (insulin mobilization, microtubule dependence) are “data not shown.”
- Evident: findings rely on rodent optic nerve/spinal cord and cultured oligodendrocytes; axonal energy metabolism is inferred from conduction recovery and lactate rescue rather than direct ATP measurement; no human data are presented.
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53 Own result · 13 Own interpretation · 11 Not checked yet · 5 Own method · 2 No basis given
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“that was efficiently blocked by D-(−)-2-amino-5-phosphonopentanoic acid (D-AP5)”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > NMDA Receptor Activation Triggers GLUT1 Surface Expression and Enhances Glucose Import in Cultured Oligodendrocytes
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“Activation of NMDA receptors caused a significantly increased FRET signal”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > NMDA Receptor Activation Triggers GLUT1 Surface Expression and Enhances Glucose Import in Cultured Oligodendrocytes
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“whereas the abundance of MCT1 was the same”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > NMDA Receptor Activation Triggers GLUT1 Surface Expression and Enhances Glucose Import in Cultured Oligodendrocytes
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“we calculated a 24% ± 4% increase of U-13C-lactate release originating from U-13C6-labeled glucose”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > NMDA Receptor Activation Triggers GLUT1 Surface Expression and Enhances Glucose Import in Cultured Oligodendrocytes
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“that was abolished by 7-CKA and D-AP5”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > NMDA Receptor Activation Triggers GLUT1 Surface Expression and Enhances Glucose Import in Cultured Oligodendrocytes
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“revealing a 2-fold GLUT1 increase at the cell surface following 30 min NMDA stimulation”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > NMDA Receptor Activation Triggers GLUT1 Surface Expression and Enhances Glucose Import in Cultured Oligodendrocytes
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“quantified the uptake of 2-deoxyglucose (2DG) to confirm that NMDA elevates glucose import”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > NMDA Receptor Activation Triggers GLUT1 Surface Expression and Enhances Glucose Import in Cultured Oligodendrocytes
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“there were no signs of oligodendrocyte death”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > NMDA Receptor Activation Triggers GLUT1 Surface Expression and Enhances Glucose Import in Cultured Oligodendrocytes
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“In contrast, monocarboxylate transporter MCT1 distribution was unaffected by NMDA”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > NMDA Receptor Activation Triggers GLUT1 Surface Expression and Enhances Glucose Import in Cultured Oligodendrocytes
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“NR1 was lost by immunostaining, as shown for optic nerve”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > Myelination In Vivo in the Absence of Oligodendroglial NMDA Receptors
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“i.e., 0.56 ± 0.04 mM at baseline and 1.85 ± 0.24 mM following NMDA receptor stimulation”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > NMDA Receptor Activation Triggers GLUT1 Surface Expression and Enhances Glucose Import in Cultured Oligodendrocytes
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“Remarkably, treatment with NMDA triggered GLUT1 redistribution in oligodendrocytes within 30 min, leading to apparent surface expression”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > NMDA Receptor Activation Triggers GLUT1 Surface Expression and Enhances Glucose Import in Cultured Oligodendrocytes
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“at P10, when many oligodendrocytes had matured and express Cnp1, about one-third of the floxed alleles were excised, and recombination reached 62% ± 8% at P96”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > Myelination In Vivo in the Absence of Oligodendroglial NMDA Receptors
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“At the age of 19 months, NR1 mutants exhibited a severe neurological phenotype including hind limb clasping, hunchback, and ataxia”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > In Vivo Relevance of Oligodendroglial NMDA Receptor Function
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“While most white and gray matter regions in mutant mice, including optic nerves, appeared devoid of pathology within the first year (data not shown), such changes became detectable in white matter tracts of the medulla”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > In Vivo Relevance of Oligodendroglial NMDA Receptor Function
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“we observed myelin delamination and degenerating axons in cervical spinal cord sections”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > In Vivo Relevance of Oligodendroglial NMDA Receptor Function
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“We detected no overt differences between NR1 mutants and controls in spinal conduction properties or axon excitability”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > In Vivo Relevance of Oligodendroglial NMDA Receptor Function
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“we found no difference in the onset of EAE symptoms or in clinical severity”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > Causality of NMDA Receptor Signaling and Glucose Metabolism in Axonal Support
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“we noted at ages P18–P20 that myelin was thinner, with fewer myelinated axons in the mutant optic nerves”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > Myelination In Vivo in the Absence of Oligodendroglial NMDA Receptors
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“all optic nerves maintained conductivity (defined as “CAP area” of 1.0) and, within minutes after OGD onset, displayed block of nerve conduction”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > Functional Analysis of Myelinated Axons
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“This difference was only transient as adult (P70) NR1 mutant optic nerves “catch up” and exhibit a normal myelin sheath thickness”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > Myelination In Vivo in the Absence of Oligodendroglial NMDA Receptors
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“in the absence of free extracellular Ca2+, the axonal recovery was almost 100% in control nerves yet remained significantly impaired in NR1 mutants”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > Causality of NMDA Receptor Signaling and Glucose Metabolism in Axonal Support
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“CAP profiles revealed a transiently reduced conduction velocity, again only at the peak of myelination (age P19–P21) and mainly affecting small caliber axons”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > Functional Analysis of Myelinated Axons
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“using lactate-containing ACSF for reperfusion, optic nerves from NR1 mutants recovered as well as control nerves and even better than in the presence of glucose”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > Causality of NMDA Receptor Signaling and Glucose Metabolism in Axonal Support
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“In purified myelin from mutant brains, we found a strong reduction of GLUT1 (but not MCT1) compared to controls”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > Myelination In Vivo in the Absence of Oligodendroglial NMDA Receptors
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“mutant mice were normally developed with functional white matter tracts, as shown for the optic nerve”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > Myelination In Vivo in the Absence of Oligodendroglial NMDA Receptors
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“when triggered with NMDA, trafficking was expectedly calcium dependent and required a stable microtubule network”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > DISCUSSION
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“Most likely, membrane repolarization (triggered by NMDA receptor signaling and ion influx) consumes the additional ATP and leads to more glycolysis with lactate release.”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > NMDA Receptor Activation Triggers GLUT1 Surface Expression and Enhances Glucose Import in Cultured Oligodendrocytes
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“Thus, further loss of axonal conductivity was not caused by more severe myelin injury, but rather by less-efficient axonal recovery from the metabolic stress of OGD.”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > Functional Analysis of Myelinated Axons
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In the paper
“In development, NMDA receptors are most abundant in oligodendrocyte precursors”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > DISCUSSION
What the sources say
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In the paper
“In myelin, NR1 is associated with NR2C and NR3A subunits that provide a weak Mg2+ block”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > DISCUSSION
What the sources say
- Not checked yetcites Burzomato et al., 2010 source
- Not checked yetcites Das et al., 1998
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“suggesting that axons require oligodendroglial support mostly after myelination, which limits rapid axonal access to extracellular metabolites”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > Functional Analysis of Myelinated Axons
What the sources say
- Not checked yetcites Nave, 2010 source
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“These are best explained by the delay of CNS myelination”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > Functional Analysis of Myelinated Axons
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“caused by ongoing neurodegeneration, which became visible at 10 months”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > RESULTS > In Vivo Relevance of Oligodendroglial NMDA Receptor Function
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In the paper
“For quantification, 10–12 randomly taken images from three controls and three NR1 mutants were assessed.”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > EXPERIMENTAL PROCEDURES > Immunoelectron Microscopy
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In the paper
“Oligodendroglial NMDA receptors are localized in specialized microdomains of myelinating processes”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > DISCUSSION
What the sources say
- Not checked yetcites Stirling and Stys, 2010
- Not checked yetcites Stys, 2011 source
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“They have direct access to the vasculature, store glycogen, and rapidly respond to energy deprivation with glycogen breakdown”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > DISCUSSION
What the sources say
- Not checked yetcites Brown and Ransom, 2007
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“For g-ratio analysis, 4–5 random overview pictures were taken at 8,000× magnification, 200 axons analyzed using ImageJ (images were blinded for experimenter).”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > EXPERIMENTAL PROCEDURES > Electron Microscopy and Morphometry
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“OPCs utilized for biotinylation assays, 2-deoxyglucose uptake, or lactate release were further purified to 98.2% ± 0.3% by negative selection immunopanning (Barres et al., 1992).”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > EXPERIMENTAL PROCEDURES > Cell Culture Preparation
What the sources say
- Not checked yetcites Barres et al., 1992 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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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
“For analysis of unmyelinated, myelinated, and ensheathed axons (defined as 1–3 uncompacted layers), 4–6 EM images with 12,000× magnification 400–700 axons were counted for each nerve.”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > EXPERIMENTAL PROCEDURES > Electron Microscopy and Morphometry
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.
In the paper
“astrocytes can also support axon function by releasing lactate in the white matter”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > DISCUSSION
What the sources say
- Not checked yetcites Brown and Ransom, 2007
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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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
“Three individual experiments with 14–24 cells per condition were analyzed.”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > EXPERIMENTAL PROCEDURES > Immunocytochemistry
plainn = 3- 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
“After OGD control ACSF and O2 were restored and CAPs were recorded for up to 2–3 hr, responses were stabilized within 20 to 30 min.”
§ Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism > EXPERIMENTAL PROCEDURES > Optic Nerve Recordings
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
The average spike count rate is the key determinant of axonal ATP consumption.
“Since the average spike count rate is the key determinant of axonal ATP consumption”
The paper relies on this without support.
Constitutive overproduction of lactate would result in lactic acidosis detrimental for white matter function.
“The constitutive overproduction of lactate would result in lactic acidosis, detrimental for white matter function.”
The paper relies on this without support.
Oligodendrocytes need to know the spiking activity of myelinated axons to adapt their own energy metabolism.
“oligodendrocytes need to “know” the spiking activity of myelinated axons”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The model is further supported by ex vivo electrophysiological recordings of compound action potentials in optic nerves under defined metabolic conditions and with the help of neuronally expressed ATP sensors (Saab et al., 2016;Trevisiol et al., 2017).”
From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Saab et al., 2016
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“that recombines floxed genes to virtually 100% in oligodendrocytes and up to 60% of OPCs (Madsen et al., 2016;Saab et al., 2016;Vajda et al., 2015).”
From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Saab et al., 2016
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“we turned to the analysis of the optic nerve, a well-myelinated white matter tract, in which all Cnp Cre recombined cells are of oligodendroglial origin (Saab et al., 2016).”
From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Saab et al., 2016
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“As oligodendrocytes support axonal energy metabolism and neuronal health4–7, we hypothesized that loss of myelin integrity could be an upstream risk factor for neuronal amyloid-β (Aβ) deposition, the central neuropathological hallmark of AD.”
From Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease (2023) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“This opens the possibility that glycolytic oligodendrocytes, which are suggested to support electrically active axons with an excess of glycolysis products (Fünfschilling et al., 2012;Lee et al., 2012;Saab et al., 2016;Trevisiol et al., 2017) do so primarily by self-made pyruvate.”
From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Saab et al., 2016
In the citing paper
“Either glucose or lactate can be used as an energy source for white matter (Brown et al., 2001; Saab et al., 2016),”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Saab et al., 2016
Citations
Cites
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InfluentialPreparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue.
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InfluentialOligodendroglia metabolically support axons and contribute to neurodegeneration
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“This confirms that axons readily use lactate for ATP generation (Fünfschilling et al., 2012; Lee et al., 2012; Tekkök et al., 2005; Wyss et al., 2011).”
InfluentialGlycolytic oligodendrocytes maintain myelin and long-term axonal integrity
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“This confirms that axons readily use lactate for ATP generation (Fünfschilling et al., 2012; Lee et al., 2012; Tekkök et al., 2005; Wyss et al., 2011).”
InfluentialSelf-citationNeuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain
Gibson, E. M., Purger, D., Mount, C. W., Goldstein, A. K., Lin, G. L., Wood, L. S., Inema, I., Miller, S. E., Bieri, G., Zuchero, J. B., et al. (2014) · Science · doi:10.1126/science.1252304 · Cited by 1,472 · cited 2×
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MYELINATION IN RAT BRAIN: METHOD OF MYELIN ISOLATION1
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InfluentialCell death and control of cell survival in the oligodendrocyte lineage
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InfluentialDisruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination
Lappe-Siefke, C., Goebbels, S., Gravel, M., Nicksch, E., Lee, J., Braun, P. E., Griffiths, I. R., & Nave, K.-A. (2003) · Nature Genetics · doi:10.1038/ng1095 · Cited by 1,036 · cited 8×
“Oligodendroglial metabolic support can explain why myelinated axons are vitally dependent on myelin integrity, independent of the myelin function in saltatory conduction (Griffiths et al., 1998; Kassmann et al., 2007; Lappe-Siefke et al., 2003).”
InfluentialSelf-citationMyelination of the Nervous System: Mechanisms and Functions
Nave, K.-A., & Werner, H. B. (2014) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100913-013101 · Cited by 983
Self-citationAxonal Swellings and Degeneration in Mice Lacking the Major Proteolipid of Myelin
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“Oligodendroglial metabolic support can explain why myelinated axons are vitally dependent on myelin integrity, independent of the myelin function in saltatory conduction (Griffiths et al., 1998; Kassmann et al., 2007; Lappe-Siefke et al., 2003).”
InfluentialSelf-citationNMDA receptors are expressed in oligodendrocytes and activated in ischaemia
Káradóttir, R. T., Cavelier, P., Bergersen, L. H., & Attwell, D. (2005) · Nature · doi:10.1038/nature04302 · Cited by 773 · cited 3×
“While NMDA receptors are widely studied in glutamatergic neurotransmission, the role of NMDA receptors in oligodendrocytes has remained enigmatic (De Biase et al., 2011; Guo et al., 2012; Káradóttir et al., 2005; Li et al., 2013; Lipton, 2006; Lundgaard et al., 2013; Micu et al., 2006; Piña-Crespo et al., 2010; Salter…”
Impaired adult myelination in the prefrontal cortex of socially isolated mice
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“…signaling in oligodendrocyte differentiation and promoting myelinationhasbeensuggested, basedon in vitroobservations (Li et al., 2013; Lundgaard et al., 2013), which is compatible with neuronal activity stimulating OPC proliferation and myelination in vivo (Gibson et al., 2014; Liu et al., 2012).”
Regulation of oligodendrocyte differentiation and myelination
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“Oligodendrocytes, best known for making myelin (Emery, 2010; Nave and Werner, 2014), also support the survival of myelinated axons (Griffiths et al.”
Myelination and the trophic support of long axons
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“Importantly, axonal recovery after OGD was normal prior to age P10 (Figure S6A), suggesting that axons require oligodendroglial support mostly after myelination, which limits rapid axonal access to extracellular metabolites (Nave, 2010).”
Self-citationControl of local protein synthesis and initial events in myelination by action potentials
Wake, H., Lee, P. R., & Fields, R. D. (2011) · Science · doi:10.1126/science.1206998 · Cited by 636
Astrocyte glycogen and brain energy metabolism
Brown, A. M., & Ransom, B. R. (2007) · Glia · doi:10.1002/glia.20557 · Cited by 626 · cited 2×
“They have direct access to the vasculature, store glycogen, and rapidly respond to en- ergy deprivation with glycogen breakdown (Brown and Ransom, 2007).”
Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A
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“is associated with NR2C and NR3A subunits that provide a weak Mg block (Burzomato et al., 2010; Das et al., 1998), suggesting that calcium entry does not require prior membrane depolarization.”
NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury
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“While NMDA receptors are widely studied in glutamatergic neurotransmission, the role of NMDA receptors in oligodendrocytes has remained enigmatic (De Biase et al., 2011; Guo et al., 2012; Káradóttir et al., 2005; Li et al., 2013; Lipton, 2006; Lundgaard et al., 2013; Micu et al., 2006; Piña-Crespo et al., 2010; Salter…”
InfluentialRole for Human SIRT2 NAD-Dependent Deacetylase Activity in Control of Mitotic Exit in the Cell Cycle
Dryden, S. C., Nahhas, F. A., Nowak, J. E., Goustin, A. S., & Tainsky, M. A. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.9.3173-3185.2003 · Cited by 506 · cited 1×
“…were separated on 10% SDS-polyacrylamide gels, blotted onto polyvinylidene difluoride membranes (Roche), and incubated with primary antibodies for GLUT1 (1:500, Abcam Cat# ab32551 RRID: AB_732605), MCT1 (1:1,000, Millipore Cat# AB1286 RRID: AB_90565), and SIRT2 (1:2,000) (Dryden et al., 2003).”
NMDA receptors mediate calcium accumulation in myelin during chemical ischaemia
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“Oligodendroglial NMDA receptors are localized in special- ized microdomains of myelinating processes (Stirling and Stys, 2010; Stys, 2011) and also face the periaxonal space (Micu et al., 2006).”
InfluentialVesicular release of glutamate from unmyelinated axons in white matter
Ziskin, J. L., Nishiyama, A., Rubio, M. E., Fukaya, M., & Bergles, D. E. (2007) · Nature Neuroscience · doi:10.1038/nn1854 · Cited by 488 · cited 2×
“Like unmyelinated axons (Kukley et al., 2007;Wakeet al., 2011; Ziskin et al., 2007) alsomyelinated axons release glutamate upon spiking, which induces calcium elevations in myelin (Micu et al.”
Myelin Membrane Wrapping of CNS Axons by PI(3,4,5)P3-Dependent Polarized Growth at the Inner Tongue
Snaidero, N., Möbius, W., Czopka, T., Hekking, L. H. P., Mathisen, C., Verkleij, D., Goebbels, S., Edgar, J. M., Merkler, D., Lyons, D. A., et al. (2014) · Cell · doi:10.1016/j.cell.2013.11.044 · Cited by 477 · cited 4×
“Myelin is assembled as a spiral extension of oligo- dendroglial cell membrane, which requires vesicular transport of membrane material through non-compacted cytosolic chan- nels to the growing tip (Snaidero et al., 2014).”
InfluentialSelf-citationVesicular glutamate release from axons in white matter
Kukley, M., Capetillo‐Zarate, E., & Dietrich, D. (2007) · Nature Neuroscience · doi:10.1038/nn1850 · Cited by 472 · cited 2×
“Like unmyelinated axons (Kukley et al., 2007;Wakeet al., 2011; Ziskin et al., 2007) alsomyelinated axons release glutamate upon spiking, which induces calcium elevations in myelin (Micu et al.”
In Vivo Evidence for Lactate as a Neuronal Energy Source
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“This confirms that axons readily use lactate for ATP generation (Fünfschilling et al., 2012; Lee et al., 2012; Tekkök et al., 2005; Wyss et al., 2011).”
Regulation of Oligodendrocyte Development and Myelination by Glucose and Lactate
Rinholm, J. E., Hamilton, N. B., Kessaris, N., Richardson, W. D., Bergersen, L. H., & Attwell, D. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3516-10.2011 · Cited by 383 · cited 4×
“Glucose is amajor carbon source for lipid precursor metabolites, which are rate-limiting for myelination (Rinholm et al., 2011). ptake by Cultured Oligodendrocytes ulation mobilizes GLUT1 and increases its cell surface expression, which is panned NMDA-treated oligodendrocytes and controls. ea of n…”
InfluentialAxonal loss and neuroinflammation caused by peroxisome-deficient oligodendrocytes
Kassmann, C. M., Lappe-Siefke, C., Baes, M., Brügger, B., Mildner, A., Werner, H. B., Natt, O., Michaelis, T., Prinz, M., Frahm, J., et al. (2007) · Nature Genetics · doi:10.1038/ng2070 · Cited by 357 · cited 4×
“Oligodendroglial metabolic support can explain why myelinated axons are vitally dependent on myelin integrity, independent of the myelin function in saltatory conduction (Griffiths et al., 1998; Kassmann et al., 2007; Lappe-Siefke et al., 2003).”
InfluentialSelf-citationNeuregulin and BDNF Induce a Switch to NMDA Receptor-Dependent Myelination by Oligodendrocytes
Lundgaard, I., Luzhynskaya, A., Stockley, J. H., Wang, Z., Evans, K. A., Swire, M., Volbracht, K., Gautier, H. O. B., Franklin, R. J. M., ffrench‐Constant, C., et al. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001743 · Cited by 351 · cited 3×
“The developmental delay of myelination in NR1 mutant optic nerves fits well the unex- plained observation that demyelinating lesions repair less well when NMDA receptors are blocked (Li et al., 2013; Lundgaard et al., 2013).”
Takanaga, H., Chaudhuri, B., & Frommer, W. B. (2008) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2007.11.015 · Cited by 338 · cited 4×
“To determine functional GLUT1 insertion, we expressed a glucose sensor (Ta- kanaga et al., 2008) in transfected oligodendrocytes (Figure 1E).”
InfluentialThe role of myelin and oligodendrocytes in axonal energy metabolism
Saab, A. S., Tzvetanova, I. D., & Nave, K.-A. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.09.008 · Cited by 324 · cited 2×
“However, the concept of glycolytic support by oligodendrocytes (Morrison et al., 2013; Saab et al., 2013) rai- ses the question of how glucose utilization is quantitatively regu- lated.”
Self-citationWhy do axons differ in caliber?
Perge, J., Niven, J., Mugnaini, E., Balasubramanian, V., & Sterling, P. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.4254-11.2012 · Cited by 318 · cited 6×
“126 Neuron 91, 119–132, July 6, 2016 The majority of myelinated axons in cortico-spinal tracts fire at a high frequency and comprise a high energy demanding white matter tract (Perge et al., 2012).”
InfluentialMiller, R. H., David, S., Patel, R., Abney, E. R., & RAFF, M. C. (1985) · Developmental Biology · doi:10.1016/0012-1606(85)90432-4 · Cited by 316 · cited 2×
“However, at P10, when many oligodendrocytes had matured and express Cnp1, about one-third of the floxed alleles were excised, and recombination reached 62% ± 8% at P96, when myelination is completed, matching the expected proportion of oligodendrocyte in adult optic nerves (Miller et al., 1985).”
Excitability and synaptic communication within the oligodendrocyte lineage
De Biase, L. M., Nishiyama, A., & Bergles, D. E. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.6000-09.2010 · Cited by 286 · cited 1×
“In development, NMDA receptors are most abundant in oligodendrocyte precursors (De Biase et al., 2010; Zhang et al., 2014).”
Oligodendroglia: metabolic supporters of axons
Morrison, B. M., Lee, Y., & Rothstein, J. D. (2013) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.07.007 · Cited by 262 · cited 2×
“However, the concept of glycolytic support by oligodendrocytes (Morrison et al., 2013; Saab et al., 2013) rai- ses the question of how glucose utilization is quantitatively regu- lated.”
Proteolipid Protein Is Required for Transport of Sirtuin 2 into CNS Myelin
Werner, H. B., Kuhlmann, K., Shen, S., Uecker, M., Schardt, A., Dimova, K. P., Orfaniotou, F., Dhaunchak, A. S., Brinkmann, B. G., Möbius, W., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1254-07.2007 · Cited by 257 · cited 1×
“Immunoblotting was performed as described before (Werner et al., 2007).”
Self-citationTekkök, S. B., Brown, A. M., Westenbroek, R., Pellerin, L., & Ransom, B. R. (2005) · Journal of Neuroscience Research · doi:10.1002/jnr.20573 · Cited by 224 · cited 1×
“This confirms that axons readily use lactate for ATP generation (Fünfschilling et al., 2012; Lee et al., 2012; Tekkök et al., 2005; Wyss et al., 2011).”
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“130 Neuron 91, 119–132, July 6, 2016 CAP area is proportional to the total number of excited axons (Stys et al., 1991).”
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“In the rodent optic nerve, the highest myelination rate occurs during the third postnatal week (Hildebrand and Waxman, 1984) and predicts the highest demands for glucose as a carbon source for lipid synthesis at this time.”
Mechanisms of axonal injury: internodal nanocomplexes and calcium deregulation
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“During OGD, abnormal Ca entry into the axonal compartment triggers axon loss probably resulting from excessive glutamate signaling caused by reversal of glutamate transporters (Stirling and Stys, 2010; Tekkök et al., 2007).”
De Biase, L. M., Kang, S. H., Baxi, E. G., Fukaya, M., Pucak, M. L., Mishina, M., Calabresi, P. A., & Bergles, D. E. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.2455-11.2011 · Cited by 161 · cited 4×
“Unfortunately, the early functions of glutamate signaling were not revealed by the deletion of NR1 in OPC (De Biase et al., 2011; Guo et al., 2012).”
InfluentialProton-gated Ca2+-permeable TRP channels damage myelin in conditions mimicking ischaemia
Hamilton, N. B., Kołodziejczyk, K., Kougioumtzidou, E., & Attwell, D. (2016) · Nature · doi:10.1038/nature16519 · Cited by 159 · cited 1×
“, 2006; Salter and Fern, 2005) may not be the main mechanism causing myelin damage (Hamilton et al., 2016).”
High resolution measurement of the glycolytic rate
Bittner, C. X. (2010) · Frontiers in Neuroenergetics · doi:10.3389/fnene.2010.00026 · Cited by 150 · cited 1×
“For control experiments and sensor calibration (Bittner et al., 2010), cells were incubated without glucose or adding either iodoacetate (glycolysis inhibitor, 1 mM) or cytochalasin B (glucose transporter blocker, 40 mM).”
Li, C., Xiao, L., Liu, X., Yang, W., Shen, W., Hu, C., Yang, G., & He, C. (2013) · Glia · doi:10.1002/glia.22469 · Cited by 144 · cited 6×
“A role for NMDA re- ceptor signaling in oligodendrocyte differentiation and promoting myelinationhasbeensuggested, basedon in vitroobservations (Li et al., 2013; Lundgaard et al., 2013), which is compatible with neuronal activity stimulating OPC proliferation and myelination in vivo (Gibson et al.,…”
InfluentialThe molecular physiology of the axo-myelinic synapse
Micu, I., Plemel, J. R., Lachance, C., Proft, J., Jansen, A. J., Cummins, K., van Minnen, J., & Stys, P. K. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2015.10.006 · Cited by 140 · cited 4×
“Recently, axonal activity was shown to induce NMDA receptor-mediated calcium increases in myelin, indicating that adult oligodendrocytes have functional NMDA receptors (Micu et al., 2016).”
InfluentialWhite Matter Vulnerability to Ischemic Injury Increases with Age Because of Enhanced Excitotoxicity
Baltan, S., Besancon, E., Mbow, B., Ye, Z., Hamner, M. A., & Ransom, B. R. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5137-07.2008 · Cited by 132 · cited 1×
“For oxygen-glucose deprivation (OGD), the protocol was performed as described previously (Baltan et al., 2008).”
Self-citationBiogenesis and regulation of insulin-responsive vesicles containing GLUT4
Bogan, J. S., & Kandror, K. V. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2010.03.012 · Cited by 129 · cited 2×
“Is NMDA receptor-dependent regulation of GLUT1 in oligodendrocytes and the non-compacted myelin compartment the same as GLUT4 regulation in other cell types (Bogan and Kandror, 2010)? In adipocytes, insulin-dependent GLUT4 trafficking requires calcium-dependent myosin motors (Yip et al.”
Excitotoxic Mechanisms of Ischemic Injury in Myelinated White Matter
Tekkök, S. B., Ye, Z., & Ransom, B. R. (2007) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600455 · Cited by 129 · cited 6×
“Next, we examined myelinated optic nerves under metabolic stress for their ability to recover from transient oxygen-glucose deprivation (OGD), a well-established model of acute ischemia (Tekkök et al., 2007).”
InfluentialYip, M. F., Ramm, G., Larance, M., Hoehn, K. L., Wagner, M. C., Guilhaus, M., & James, D. E. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.09.011 · Cited by 126 · cited 2×
“In adipocytes, insu- lin-dependent GLUT4 trafficking requires calcium-depen- dent myosin motors (Yip et al., 2008).”
Electron Microscopy of the Mouse Central Nervous System
Möbius, W., Cooper, B. H., Kaufmann, W. A., Imig, C., Ruhwedel, T., Snaidero, N., Saab, A. S., & Varoqueaux, F. (2010) · Methods in cell biology · doi:10.1016/s0091-679x(10)96020-2 · Cited by 116 · cited 2×
“Optic nerves were acutely removed and either immersion-fixed for conventional sample preparation or cryofixed by HPF and freeze substituted as described in detail (Möbius et al., 2010).”
Self-citationActivity-Dependent Regulation of Surface Glucose Transporter-3
Ferreira, J. M., Burnett, A. L., & Rameau, G. A. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.1850-09.2011 · Cited by 115 · cited 2×
“Cultured neurons mobilize glucose transporter GLUT3 in response to glutamate (Ferreira et al., 2011).”
Excitatory Glycine Responses of CNS Myelin Mediated by NR1/NR3 “NMDA” Receptor Subunits
Piña-Crespo, J., Talantova, M. V., Micu, I., States, B. A., Chen, H.-S. V., Tu, S., Nakanishi, N., Tong, G., Zhang, D., Heinemann, S. F., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1593-10.2010 · Cited by 102 · cited 2×
“While NMDA receptors are widely studied in glutamatergic neurotransmission, the role of NMDA receptors in oligodendrocytes has remained enigmatic (De Biase et al., 2011; Guo et al., 2012; Káradóttir et al., 2005; Li et al., 2013; Lipton, 2006; Lundgaard et al., 2013; Micu et al., 2006; Piña-Crespo et al., 2010; Salter…”
NMDA Receptors, Glial Cells, and Clinical Medicine
Lipton, S. A. (2006) · Neuron · doi:10.1016/j.neuron.2006.03.026 · Cited by 92 · cited 2×
“While NMDA receptors are widely studied in glutamatergic neurotransmission, the role of NMDA receptors in oligodendrocytes has remained enigmatic (De Biase et al., 2011; Guo et al., 2012; Káradóttir et al., 2005; Li et al., 2013; Lipton, 2006; Lundgaard et al., 2013; Micu et al., 2006; Piña-Crespo et al., 2010; Salter…”
β1 integrins are required for normal CNS myelination and promote AKT-dependent myelin outgrowth
Barros, C. S., Nguyen, T., Spencer, K. S. R., Nishiyama, A., Colognato, H., & Müller, U. (2009) · Development · doi:10.1242/dev.038679 · Cited by 87 · cited 2×
“Cell Culture Preparation Primary mouse or rat oligodendrocyte progenitor cells (OPCs) were isolated from cerebral cortices at P0–P2 as described previously (Barros et al., 2009; McCarthy and de Vellis, 1980).”
Calcium dyshomeostasis in white matter pathology
Matute, C. (2009) · Cell Calcium · doi:10.1016/j.ceca.2009.12.004 · Cited by 81 · cited 1×
“Here, we found no difference in the onset of EAE symptoms or in clinical severity (Figures S5B–S5D), as indicated earlier (Guo et al., 2012; Matute, 2010).”
Self-citationBurzomato, V., Frugier, G., Pérez-Otaño, I., Kittler, J. T., & Attwell, D. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.195503 · Cited by 78 · cited 2×
“is associated with NR2C and NR3A subunits that provide a weak Mg block (Burzomato et al., 2010; Das et al., 1998), suggesting that calcium entry does not require prior membrane depolarization.”
Guo, F., Maeda, Y., Ko, E. M., Delgado, M., Horiuchi, M., Soulika, A., Miers, L., Burns, T., Itoh, T., Shen, H., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.4073-11.2012 · Cited by 76 · cited 9×
“This suggests that NMDA receptors are not essential for myelination per se, in agreement with earlier reports (De Biase et al., 2011; Guo et al., 2012).”
InfluentialStys, P. K. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.06.004 · Cited by 51 · cited 4×
“Oligodendroglial NMDA receptors are localized in specialized microdomains of myelinating processes (Stirling and Stys, 2010; Stys, 2011) and also face the periaxonal space (Micu et al.”
InfluentialBarry, J. M. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00153 · Cited by 49 · cited 2×
“Since the average spike count rate is the key determinant of axonal ATP consumption, oligodendrocytes need to ‘‘know’’ the spiking activity of myelinated axons, which can differ greatly in vivo (Barry, 2015; Perge et al., 2012).”
Novel hypoglycemic injury mechanism: N‐methyl‐D‐aspartate receptor–mediated white matter damage
Yang, X., Hamner, M. A., Brown, A. M., Evans, R. D., Ye, Z., Chen, S., & Ransom, B. R. (2013) · Annals of Neurology · doi:10.1002/ana.24050 · Cited by 26 · cited 2×
“While NMDA receptors are widely studied in glutamatergic neurotransmission, the role of NMDA receptors in oligodendrocytes has remained enigmatic (De Biase et al., 2011; Guo et al., 2012; Káradóttir et al., 2005; Li et al., 2013; Lipton, 2006; Lundgaard et al., 2013; Micu et al., 2006; Piña-Crespo et al., 2010; Salter…”
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Magistretti, P. J., & Allaman, I. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2018.19 · Cited by 1,298
Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing
Cunnane, S. C., Trushina, E., Morland, C., Prigione, A., Casadesus, G., Andrews, Z. B., Beal, M. F., Bergersen, L. H., Brinton, R. D., de la Monte, S., et al. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0072-x · Cited by 1,003
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Feldman, E. L., Nave, K.-A., Jensen, T. S., & Bennett, D. L. H. (2017) · Neuron · doi:10.1016/j.neuron.2017.02.005 · Cited by 915
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Stadelmann, C., Timmler, S., Barrantes‐Freer, A., & Simons, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00031.2018 · Cited by 799
“Oligodendrocytes appear to sense the metabolic demands of axons by N-methyl-D-aspartate (NMDA) receptors that are associated with the internodal/paranodal membrane (538).”
BackgroundBrain Cell Type Specific Gene Expression and Co-expression Network Architectures
McKenzie, A. T., Wang, M., Hauberg, M. E., Fullard, J. F., Kozlenkov, A., Keenan, A., Hurd, Y. L., Dracheva, S., Casaccia, P., Roussos, P., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-27293-5 · Cited by 481
Metadata
- Authors
- Saab, A. S., Tzvetavona, I. D., Trevisiol, A., Baltan, S., Dibaj, P., Kusch, K., Möbius, W., Goetze, B., Jahn, H. M., Huang, W., Steffens, H., Schomburg, E. D., Pérez-Samartín, A., Pérez-Cerdá, F., Bakhtiari, D., Matute, C., Löwel, S., Griesinger, C., Hirrlinger, J., Kirchhoff, F., & Nave, K.-A.
- Affiliations
- University of Zurich (CH)
- Max Planck Institute of Experimental Medicine (DE)
- Cleveland Clinic (US)
- Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103 (DE)
- University of Göttingen (DE)
- Max Planck Institute for Biophysical Chemistry (DE)
- University of the Basque Country (ES)
- Corresponding author
- Kirchhoff, Frank
- Nave, Klaus-Armin
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 91
- Issue
- 1
- Pages
- 119-132
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC9084537
- OpenAlex
- W2419165202
- Semantic Scholar
- 35212334fda129fe29657b347be129741e5f6e4f
- Cited by
- 590
- References
- 60
- Citations by year
- 2026: 48 · 2025: 68 · 2024: 80 · 2023: 61 · 2022: 65 · 2021: 73 · 2020: 58 · 2019: 41 · 2018: 41 · 2017: 45 · 2016: 9
- FWCI
- 25.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- PubMed Central (acceptedVersion)
- GRO (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Institute on Aging (R56AG033720, R01AG033720)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- glucose uptake, GLUT1, axonal energy metabolism, myelin, optic nerve, oxygen-glucose deprivation, lactate, glycolysis, glutamate release, myelination
- MeSH terms
- Animals, Axons, Energy Metabolism, Glucose, Mice, Transgenic, Myelin Sheath, Oligodendroglia, Optic Nerve, Oxygen, Receptors, N-Methyl-D-Aspartate, Glucose Transporter Type 1
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