Neurons require glucose uptake and glycolysis in vivo.
CP: Neuroscience
bioenergetics
brain energy
galactose metabolism
glucose transporter
glycolysis
hyperpolarized magnetic resonance spectroscopic imaging
metabolomics
neuronal glucose metabolism
pyruvate kinase
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
25 04 2023
25 04 2023
Historique:
received:
03
01
2023
revised:
22
02
2023
accepted:
20
03
2023
medline:
4
10
2023
pubmed:
8
4
2023
entrez:
7
4
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37027294
pii: S2211-1247(23)00346-7
doi: 10.1016/j.celrep.2023.112335
pmc: PMC10556202
mid: NIHMS1895582
pii:
doi:
Substances chimiques
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
112335Subventions
Organisme : NINDS NIH HHS
ID : R01 NS102156
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA168653
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG064170
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA242379
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG073082
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG065428
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI153749
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK105550
Pays : United States
Organisme : NIA NIH HHS
ID : K01 AG078485
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG071697
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061150
Pays : United States
Organisme : NCRR NIH HHS
ID : C06 RR018928
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests M.G.V.H. discloses that he is a scientific advisor for Agios Pharmaceuticals, iTeos Therapeutics, Sage Therapeutics, Faeth Therapeutics, DRIOA Ventures, and Auron Therapeutics. Y.H. discloses that he is a co-founder and scientific advisory board member of GABAeron.
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