{"PubmedArticle":{"MedlineCitation":{"@attributes":{"Status":"MEDLINE","Owner":"NLM","IndexingMethod":"Automated"},"PMID":{"@attributes":{"Version":"1"},"@text":"37027294"},"DateCompleted":{"Year":"2023","Month":"10","Day":"04"},"DateRevised":{"Year":"2025","Month":"01","Day":"15"},"Article":{"@attributes":{"PubModel":"Print-Electronic"},"Journal":{"ISSN":{"@attributes":{"IssnType":"Electronic"},"@text":"2211-1247"},"JournalIssue":{"@attributes":{"CitedMedium":"Internet"},"Volume":"42","Issue":"4","PubDate":{"Year":"2023","Month":"Apr","Day":"25"}},"Title":"Cell reports","ISOAbbreviation":"Cell Rep"},"ArticleTitle":"Neurons require glucose uptake and glycolysis in\u00a0vivo.","Pagination":{"StartPage":"112335","MedlinePgn":"112335"},"ELocationID":[{"@attributes":{"EIdType":"doi","ValidYN":"Y"},"@text":"10.1016\/j.celrep.2023.112335"},{"@attributes":{"EIdType":"pii","ValidYN":"Y"},"@text":"S2211-1247(23)00346-7"}],"Abstract":{"AbstractText":["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\u00a0vivo and require glycolysis for normal function."],"CopyrightInformation":"Copyright \u00a9 2023 The Authors. Published by Elsevier Inc. All rights reserved."},"AuthorList":{"@attributes":{"CompleteYN":"Y"},"Author":[{"@attributes":{"ValidYN":"Y"},"LastName":"Li","ForeName":"Huihui","Initials":"H","AffiliationInfo":[{"Affiliation":"Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Guglielmetti","ForeName":"Caroline","Initials":"C","AffiliationInfo":[{"Affiliation":"Department of Physical Therapy and Rehabilitation Science, San Francisco, CA 94158, USA; Department of Radiology and Biomedical Imaging, San Francisco, CA 94158, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Sei","ForeName":"Yoshitaka J","Initials":"YJ","AffiliationInfo":[{"Affiliation":"Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Zilberter","ForeName":"Misha","Initials":"M","AffiliationInfo":[{"Affiliation":"Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Le Page","ForeName":"Lydia M","Initials":"LM","AffiliationInfo":[{"Affiliation":"Department of Physical Therapy and Rehabilitation Science, San Francisco, CA 94158, USA; Department of Radiology and Biomedical Imaging, San Francisco, CA 94158, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Shields","ForeName":"Lauren","Initials":"L","AffiliationInfo":[{"Affiliation":"Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA; Graduate Program in Biomedical Sciences, University of California San Francisco, San Francisco, CA 94143, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Yang","ForeName":"Joyce","Initials":"J","AffiliationInfo":[{"Affiliation":"Graduate Program in Neuroscience, University of California San Francisco, San Francisco, CA 94158, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Nguyen","ForeName":"Kevin","Initials":"K","AffiliationInfo":[{"Affiliation":"Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Tiret","ForeName":"Brice","Initials":"B","AffiliationInfo":[{"Affiliation":"Department of Physical Therapy and Rehabilitation Science, San Francisco, CA 94158, USA; Department of Radiology and Biomedical Imaging, San Francisco, CA 94158, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Gao","ForeName":"Xiao","Initials":"X","AffiliationInfo":[{"Affiliation":"Department of Physical Therapy and Rehabilitation Science, San Francisco, CA 94158, USA; Department of Radiology and Biomedical Imaging, San Francisco, CA 94158, USA; UCSF\/UCB Graduate Program in Bioengineering, University of California San Francisco, San Francisco, CA 94158, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Bennett","ForeName":"Neal","Initials":"N","AffiliationInfo":[{"Affiliation":"Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Lo","ForeName":"Iris","Initials":"I","AffiliationInfo":[{"Affiliation":"Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Dayton","ForeName":"Talya L","Initials":"TL","AffiliationInfo":[{"Affiliation":"Koch Institute for Integrative Cancer Research and the Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Kampmann","ForeName":"Martin","Initials":"M","AffiliationInfo":[{"Affiliation":"Graduate Program in Biomedical Sciences, University of California San Francisco, San Francisco, CA 94143, USA; Graduate Program in Neuroscience, University of California San Francisco, San Francisco, CA 94158, USA; UCSF\/UCB Graduate Program in Bioengineering, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, CA, USA; Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Huang","ForeName":"Yadong","Initials":"Y","AffiliationInfo":[{"Affiliation":"Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA; Graduate Program in Biomedical Sciences, University of California San Francisco, San Francisco, CA 94143, USA; Graduate Program in Neuroscience, University of California San Francisco, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Rathmell","ForeName":"Jeffrey C","Initials":"JC","AffiliationInfo":[{"Affiliation":"Vanderbilt Center for Immunobiology, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Vander Heiden","ForeName":"Matthew","Initials":"M","AffiliationInfo":[{"Affiliation":"Koch Institute for Integrative Cancer Research and the Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Dana-Farber Cancer Institute, Boston, MA 02115, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Chaumeil","ForeName":"Myriam M","Initials":"MM","AffiliationInfo":[{"Affiliation":"Department of Physical Therapy and Rehabilitation Science, San Francisco, CA 94158, USA; Department of Radiology and Biomedical Imaging, San Francisco, CA 94158, USA; Graduate Program in Biomedical Sciences, University of California San Francisco, San Francisco, CA 94143, USA; UCSF\/UCB Graduate Program in Bioengineering, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: myriam.chaumeil@ucsf.edu."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Nakamura","ForeName":"Ken","Initials":"K","AffiliationInfo":[{"Affiliation":"Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA; Graduate Program in Biomedical Sciences, University of California San Francisco, San Francisco, CA 94143, USA; Graduate Program in Neuroscience, University of California San Francisco, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: ken.nakamura@gladstone.ucsf.edu."}]}]},"Language":["eng"],"GrantList":{"@attributes":{"CompleteYN":"Y"},"Grant":[{"GrantID":"R01 NS102156","Acronym":"NS","Agency":"NINDS NIH HHS","Country":"United States"},{"GrantID":"R01 CA168653","Acronym":"CA","Agency":"NCI NIH HHS","Country":"United States"},{"GrantID":"RF1 AG064170","Acronym":"AG","Agency":"NIA NIH HHS","Country":"United States"},{"GrantID":"R35 CA242379","Acronym":"CA","Agency":"NCI NIH HHS","Country":"United States"},{"GrantID":"P01 AG073082","Acronym":"AG","Agency":"NIA NIH HHS","Country":"United States"},{"GrantID":"R01 AG065428","Acronym":"AG","Agency":"NIA NIH HHS","Country":"United States"},{"GrantID":"R21 AI153749","Acronym":"AI","Agency":"NIAID NIH HHS","Country":"United States"},{"GrantID":"R01 DK105550","Acronym":"DK","Agency":"NIDDK NIH HHS","Country":"United States"},{"GrantID":"K01 AG078485","Acronym":"AG","Agency":"NIA NIH HHS","Country":"United States"},{"GrantID":"R01 AG071697","Acronym":"AG","Agency":"NIA NIH HHS","Country":"United States"},{"GrantID":"R01 AG061150","Acronym":"AG","Agency":"NIA NIH HHS","Country":"United States"},{"GrantID":"C06 RR018928","Acronym":"RR","Agency":"NCRR NIH HHS","Country":"United States"}]},"PublicationTypeList":{"PublicationType":[{"@attributes":{"UI":"D016428"},"@text":"Journal Article"},{"@attributes":{"UI":"D052061"},"@text":"Research Support, N.I.H., Extramural"},{"@attributes":{"UI":"D013485"},"@text":"Research Support, Non-U.S. Gov't"}]},"ArticleDate":[{"@attributes":{"DateType":"Electronic"},"Year":"2023","Month":"04","Day":"06"}]},"MedlineJournalInfo":{"Country":"United States","MedlineTA":"Cell Rep","NlmUniqueID":"101573691"},"ChemicalList":{"Chemical":[{"RegistryNumber":"IY9XDZ35W2","NameOfSubstance":{"@attributes":{"UI":"D005947"},"@text":"Glucose"}}]},"CitationSubset":["IM"],"MeshHeadingList":{"MeshHeading":[{"DescriptorName":{"@attributes":{"UI":"D006801","MajorTopicYN":"N"},"@text":"Humans"}},{"DescriptorName":{"@attributes":{"UI":"D005260","MajorTopicYN":"N"},"@text":"Female"}},{"DescriptorName":{"@attributes":{"UI":"D051379","MajorTopicYN":"N"},"@text":"Mice"}},{"DescriptorName":{"@attributes":{"UI":"D000818","MajorTopicYN":"N"},"@text":"Animals"}},{"DescriptorName":{"@attributes":{"UI":"D006019","MajorTopicYN":"Y"},"@text":"Glycolysis"},"QualifierName":[{"@attributes":{"UI":"Q000502","MajorTopicYN":"N"},"@text":"physiology"}]},{"DescriptorName":{"@attributes":{"UI":"D004734","MajorTopicYN":"Y"},"@text":"Energy Metabolism"}},{"DescriptorName":{"@attributes":{"UI":"D008279","MajorTopicYN":"N"},"@text":"Magnetic Resonance Imaging"}},{"DescriptorName":{"@attributes":{"UI":"D009474","MajorTopicYN":"N"},"@text":"Neurons"},"QualifierName":[{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D005947","MajorTopicYN":"N"},"@text":"Glucose"},"QualifierName":[{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]}]},"KeywordList":[{"@attributes":{"Owner":"NOTNLM"},"Keyword":[{"@attributes":{"MajorTopicYN":"N"},"@text":"CP: Neuroscience"},{"@attributes":{"MajorTopicYN":"N"},"@text":"bioenergetics"},{"@attributes":{"MajorTopicYN":"N"},"@text":"brain energy"},{"@attributes":{"MajorTopicYN":"N"},"@text":"galactose metabolism"},{"@attributes":{"MajorTopicYN":"N"},"@text":"glucose transporter"},{"@attributes":{"MajorTopicYN":"N"},"@text":"glycolysis"},{"@attributes":{"MajorTopicYN":"N"},"@text":"hyperpolarized magnetic resonance spectroscopic imaging"},{"@attributes":{"MajorTopicYN":"N"},"@text":"metabolomics"},{"@attributes":{"MajorTopicYN":"N"},"@text":"neuronal glucose metabolism"},{"@attributes":{"MajorTopicYN":"N"},"@text":"pyruvate kinase"}]}],"CoiStatement":"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."},"PubmedData":{"History":{"PubMedPubDate":[{"@attributes":{"PubStatus":"received"},"Year":"2023","Month":"1","Day":"3"},{"@attributes":{"PubStatus":"revised"},"Year":"2023","Month":"2","Day":"22"},{"@attributes":{"PubStatus":"accepted"},"Year":"2023","Month":"3","Day":"20"},{"@attributes":{"PubStatus":"medline"},"Year":"2023","Month":"10","Day":"4","Hour":"6","Minute":"44"},{"@attributes":{"PubStatus":"pubmed"},"Year":"2023","Month":"4","Day":"8","Hour":"6","Minute":"0"},{"@attributes":{"PubStatus":"entrez"},"Year":"2023","Month":"4","Day":"7","Hour":"12","Minute":"36"},{"@attributes":{"PubStatus":"pmc-release"},"Year":"2023","Month":"10","Day":"23"}]},"PublicationStatus":"ppublish","ArticleIdList":{"ArticleId":[{"@attributes":{"IdType":"pubmed"},"@text":"37027294"},{"@attributes":{"IdType":"mid"},"@text":"NIHMS1895582"},{"@attributes":{"IdType":"pmc"},"@text":"PMC10556202"},{"@attributes":{"IdType":"doi"},"@text":"10.1016\/j.celrep.2023.112335"},{"@attributes":{"IdType":"pii"},"@text":"S2211-1247(23)00346-7"}]},"ReferenceList":[{"Reference":[{"Citation":"B\u00e9langer M, Allaman I, and Magistretti PJ (2011). 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