Neurons require glucose uptake and glycolysis in vivo.
Neurons require large amounts of energy, but whether they can perform glycolysis or require glycolysis to maintain energy remains unclear. Using metabolomics, we show that human neurons do metabolize glucose through glycolysis and can rely on glycolysis to supply tricarboxylic acid (TCA) cycle metabolites. To investigate the requirement for glycolysis, we generated mice with postnatal deletion of either the dominant neuronal glucose transporter (GLUT3cKO) or the neuronal-enriched pyruvate kinase isoform (PKM1cKO) in CA1 and other hippocampal neurons. GLUT3cKO and PKM1cKO mice show age-dependent learning and memory deficits. Hyperpolarized magnetic resonance spectroscopic (MRS) imaging shows that female PKM1cKO mice have increased pyruvate-to-lactate conversion, whereas female GLUT3cKO mice have decreased conversion, body weight, and brain volume. GLUT3KO neurons also have decreased cytosolic glucose and ATP at nerve terminals, with spatial genomics and metabolomics revealing compensatory changes in mitochondrial bioenergetics and galactose metabolism. Therefore, neurons metabolize glucose through glycolysis in vivo and require glycolysis for normal function.
Pubmed ID: 37027294 RIS Download
Research resources used in this publication
Additional research tools detected in this publication
None foundAntibodies used in this publication
- Goat anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 594 (RRID:AB_2534095)
- Goat anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 488 (RRID:AB_2576217)
- MiTF antibody - ChIP Grade (RRID:AB_10902226)
- Anti-NeuN antibody [EPR12763] (RRID:AB_2532109)
- Anti-NeuN (RRID:AB_2298772)
- MAP2 antibody - Neuronal Marker (RRID:AB_2138153)
- PKM2 Antibody (RRID:AB_10011057)
- PKM1 (D30G6) XP Rabbit monoclonal Antibody (RRID:AB_2715534)
Associated grants
- Agency: NINDS NIH HHS, United States
Id: R01 NS102156 - Agency: NCI NIH HHS, United States
Id: R01 CA168653 - Agency: NIA NIH HHS, United States
Id: RF1 AG064170 - Agency: NCI NIH HHS, United States
Id: R35 CA242379 - Agency: NIA NIH HHS, United States
Id: P01 AG073082 - Agency: NIA NIH HHS, United States
Id: R01 AG065428 - Agency: NIAID NIH HHS, United States
Id: R21 AI153749 - Agency: NIDDK NIH HHS, United States
Id: R01 DK105550 - Agency: NIA NIH HHS, United States
Id: K01 AG078485 - Agency: NIA NIH HHS, United States
Id: R01 AG071697 - Agency: NIA NIH HHS, United States
Id: R01 AG061150 - Agency: NCRR NIH HHS, United States
Id: C06 RR018928
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This is a list of tools and resources that we have found mentioned in this publication.
Goat anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 594 (antibody)
RRID:AB_2534095
This polyclonal secondary targets IgG (H+L)
View all literature mentionsGoat anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 488 (antibody)
RRID:AB_2576217
This polyclonal secondary targets IgG (H+L)
View all literature mentionsMiTF antibody - ChIP Grade (antibody)
RRID:AB_10902226
This polyclonal targets MiTF antibody - ChIP Grade
View all literature mentionsAnti-NeuN antibody [EPR12763] (antibody)
RRID:AB_2532109
This monoclonal targets NeuN
View all literature mentionsMAP2 antibody - Neuronal Marker (antibody)
RRID:AB_2138153
This polyclonal targets MAP2 antibody - Neuronal Marker
View all literature mentionsPKM1 (D30G6) XP Rabbit monoclonal Antibody (antibody)
RRID:AB_2715534
This monoclonal targets PKM1
View all literature mentionsC57BL/6J (organism)
RRID:IMSR_JAX:000664
Mus musculus with name C57BL/6J from IMSR.
View all literature mentionsMetaMorph Microscopy Automation and Image Analysis Software (software resource)
RRID:SCR_002368
Software tool for automated microscope acquisition, device control, and image analysis. Used for integrating dissimilar fluorescent microscope hardware and peripherals into a single custom workstation, while providing all the tools needed to perform analysis of acquired images. Offers user friendly application modules for analysis such as cell signaling, cell counting, and protein expression.
View all literature mentions
