{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T09:59:11Z","timestamp":1785664751209,"version":"3.56.0"},"reference-count":64,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004836","name":"Danmarks Frie Forskningsfond","doi-asserted-by":"publisher","award":["1030-00285B"],"award-info":[{"award-number":["1030-00285B"]}],"id":[{"id":"10.13039\/501100004836","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004836","name":"Danmarks Frie Forskningsfond","doi-asserted-by":"publisher","award":["2078-00002B"],"award-info":[{"award-number":["2078-00002B"]}],"id":[{"id":"10.13039\/501100004836","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alzheimerforeningen","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is increasingly recognized as a disorder of cerebral energy metabolism, where impaired glucose utilization contributes to disease pathology. Medium-chain fatty acids (MCFAs), such as decanoic acid (C10), have emerged as promising metabolic substrates due to their ability to bypass glycolytic deficits and support mitochondrial function. In this study, we investigated the metabolic impact of C10 in the 5xFAD mouse model of AD and in human induced pluripotent stem cell (hiPSC)-derived astrocytes carrying familial AD mutations. Utilizing stable 13C-labeled metabolic tracers, we demonstrated that while [U-13C]glucose metabolism was largely preserved in cortical slices of 6-month-old 5xFAD female mice, [1,2-13C]acetate uptake was significantly reduced, suggesting impaired astrocytic metabolism. [U-13C]C10 was efficiently metabolized in both WT and 5xFAD brain slices, particularly in astrocytes, as indicated by high labeling of glutamine and citrate. Furthermore, C10 competitively inhibited glucose and acetate metabolism, suggesting its potential as an auxiliary energy substrate. In hiPSC-derived astrocytes, AD-specific metabolic responses to C10 varied by mutation, with only partial alterations in oxidative glucose metabolism observed in APP and PSEN1 variants, highlighting genotype-dependent metabolic alterations. While AD-related mutations in the hiPSC models did not lead to robust deficits, the in vivo environment in the 5xFAD model is associated with measurable metabolic changes in astrocytes. These findings underscore astrocytic metabolic dysfunction in AD and suggest that C10 supplementation may restore brain energy by supporting astrocytic oxidative metabolism.<\/jats:p>","DOI":"10.3390\/cells14242007","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T15:41:12Z","timestamp":1765899672000},"page":"2007","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Metabolic Astrocytic Support with Decanoic Acid Enhances Energy Metabolism in Alzheimer\u2019s Disease Models"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1297-3817","authenticated-orcid":false,"given":"Aishat O.","family":"Ameen","sequence":"first","affiliation":[{"name":"Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja B.","family":"Rindsh\u00f8j","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2776-2892","authenticated-orcid":false,"given":"Katarina Stoklund","family":"Dittlau","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1870 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7448-0770","authenticated-orcid":false,"given":"Karin","family":"Borges","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9480-2386","authenticated-orcid":false,"given":"Kristine K.","family":"Freude","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1870 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5027-1218","authenticated-orcid":false,"given":"Blanca I.","family":"Aldana","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark"},{"name":"Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1870 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cell.2019.09.001","article-title":"Alzheimer Disease: An Update on Pathobiology and Treatment Strategies","volume":"179","author":"Long","year":"2019","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1007\/s00259-005-1762-7","article-title":"Brain glucose metabolism in the early and specific diagnosis of Alzheimer\u2019s disease. FDG-PET studies in MCI and AD","volume":"32","author":"Mosconi","year":"2005","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41583-019-0132-6","article-title":"Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease","volume":"20","author":"Butterfield","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4899","DOI":"10.1038\/s41467-022-32592-7","article-title":"Earlier Alzheimer\u2019s disease onset is associated with tau pathology in brain hub regions and facilitated tau spreading","volume":"13","author":"Frontzkowski","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"171","DOI":"10.14283\/jpad.2023.91","article-title":"Global Energy Metabolism Deficit in Alzheimer Disease Brain","volume":"11","author":"Patel","year":"2024","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/s41573-020-0072-x","article-title":"Brain energy rescue: An emerging therapeutic concept for neurodegenerative disorders of ageing","volume":"19","author":"Cunnane","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ameen, A.O., Freude, K., and Aldana, B.I. (2022). Fats, Friends or Foes: Investigating the Role of Short- and Medium-Chain Fatty Acids in Alzheimer\u2019s Disease. Biomedicines, 10.","DOI":"10.3390\/biomedicines10112778"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"441","DOI":"10.3233\/JAD-230406","article-title":"The Effects of Medium Chain Triglyceride for Alzheimer\u2019s Disease Related Cognitive Impairment: A Systematic Review and Meta-Analysis","volume":"94","author":"Sun","year":"2023","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Giannos, P., Prokopidis, K., Lidoriki, I., Triantafyllidis, K.K., Kechagias, K.S., Celoch, K., Candow, D.G., Ostojic, S.M., and Forbes, S.C. (2022). Medium-chain triglycerides may improve memory in non-demented older adults: A systematic review of randomized controlled trials. BMC Geriatr., 22.","DOI":"10.1186\/s12877-022-03521-6"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"551","DOI":"10.3233\/JAD-180202","article-title":"Ketogenic Medium Chain Triglycerides Increase Brain Energy Metabolism in Alzheimer\u2019s Disease","volume":"64","author":"Croteau","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s11064-022-03726-6","article-title":"\u03b2-Hydroxybutyrate and Medium-Chain Fatty Acids are Metabolized by Different Cell Types in Mouse Cerebral Cortex Slices","volume":"48","author":"Andersen","year":"2023","journal-title":"Neurochem. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s13041-021-00842-2","article-title":"Astrocyte metabolism of the medium-chain fatty acids octanoic acid and decanoic acid promotes GABA synthesis in neurons via elevated glutamine supply","volume":"14","author":"Andersen","year":"2021","journal-title":"Mol. Brain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"105198","DOI":"10.1016\/j.nbd.2020.105198","article-title":"Deficient astrocyte metabolism impairs glutamine synthesis and neurotransmitter homeostasis in a mouse model of Alzheimer\u2019s disease","volume":"148","author":"Andersen","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1097\/NEN.0b013e31820e1152","article-title":"Neuronal-Astrocyte Metabolic Interactions: Understanding the Transition Into Abnormal Astrocytoma Metabolism","volume":"70","author":"Turner","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1194\/jlr.R067629","article-title":"Short- and medium-chain fatty acids in energy metabolism: The cellular perspective","volume":"57","author":"Wojtczak","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6135","DOI":"10.1038\/s41598-021-85523-9","article-title":"The medium-chain fatty acid decanoic acid reduces oxidative stress levels in neuroblastoma cells","volume":"11","author":"Mett","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1177\/0271678X16659498","article-title":"Tridecanoin is anticonvulsant, antioxidant, and improves mitochondrial function","volume":"37","author":"Tan","year":"2017","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"23617","DOI":"10.1073\/pnas.2008980117","article-title":"Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling","volume":"117","author":"Warren","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","first-page":"735","article-title":"Fatty acid transport protein expression in human brain and potential role in fatty acid transport across human brain microvessel endothelial cells","volume":"117","author":"Mitchell","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Abghari, M., Vu, J.T.C.M., Eckberg, N., Aldana, B.I., and Kohlmeier, K.A. (2023). Decanoic Acid Rescues Differences in AMPA-Mediated Calcium Rises in Hippocampal CA1 Astrocytes and Neurons in the 5xFAD Mouse Model of Alzheimer\u2019s Disease. Biomolecules, 13.","DOI":"10.3390\/biom13101461"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10129","DOI":"10.1523\/JNEUROSCI.1202-06.2006","article-title":"Intraneuronal \u03b2-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer\u2019s Disease Mutations: Potential Factors in Amyloid Plaque Formation","volume":"26","author":"Oakley","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Westi, E.W., Molhemi, S., Hansen, C.T., Skoven, C.S., Knopper, R.W., Ahmad, D.A., Rindsh\u00f8j, M.B., Ameen, A.O., Hansen, B., and Kohlmeier, K.A. (2024). Comprehensive Analysis of the 5xFAD Mouse Model of Alzheimer\u2019s Disease Using dMRI, Immunohistochemistry, and Neuronal and Glial Functional Metabolic Mapping. Biomolecules, 14.","DOI":"10.3390\/biom14101294"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1007\/s11064-016-2116-5","article-title":"Metabolic Characterization of Acutely Isolated Hippocampal and Cerebral Cortical Slices Using [U-(13)C]Glucose and [1,2-(13)C]Acetate as Substrates","volume":"42","author":"McNair","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101368","DOI":"10.1016\/j.scr.2018.101368","article-title":"Generation of two iPSC lines with either a heterozygous V717I or a heterozygous KM670\/671NL mutation in the APP gene","volume":"34","author":"Frederiksen","year":"2019","journal-title":"Stem Cell Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101403","DOI":"10.1016\/j.scr.2019.101403","article-title":"Generation of two isogenic iPSC lines with either a heterozygous or a homozygous E280A mutation in the PSEN1 gene","volume":"35","author":"Frederiksen","year":"2019","journal-title":"Stem Cell Res."},{"key":"ref_26","first-page":"e4936","article-title":"Generation of Human Induced Pluripotent Stem Cell (hiPSC)-Derived Astrocytes for Amyotrophic Lateral Sclerosis and Other Neurodegenerative Disease Studies","volume":"14","author":"Dittlau","year":"2024","journal-title":"Bio-Protocol"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.scr.2017.10.010","article-title":"Comparison of 2D and 3D neural induction methods for the generation of neural progenitor cells from human induced pluripotent stem cells","volume":"25","author":"Chandrasekaran","year":"2017","journal-title":"Stem Cell Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1002\/stem.1334","article-title":"Efficient generation of astrocytes from human pluripotent stem cells in defined conditions","volume":"31","author":"Shaltouki","year":"2013","journal-title":"Stem Cells"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1111\/jnc.16014","article-title":"Increased glucose metabolism and impaired glutamate transport in human astrocytes are potential early triggers of abnormal extracellular glutamate accumulation in hiPSC-derived models of Alzheimer\u2019s disease","volume":"168","author":"Salcedo","year":"2023","journal-title":"J. Neurochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.pnpbp.2014.10.013","article-title":"Acute anticonvulsant effects of capric acid in seizure tests in mice","volume":"57","author":"Nieoczym","year":"2015","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1016\/j.neuropharm.2011.12.015","article-title":"Anticonvulsant profile of caprylic acid, a main constituent of the medium-chain triglyceride (MCT) ketogenic diet, in mice","volume":"62","author":"Nieoczym","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Hirrlinger, J., and Waagepetersen, H.S. (2014). Metabolic Mapping of Astrocytes and Neurons in Culture Using Stable Isotopes and Gas Chromatography-Mass Spectrometry (GC-MS). Brain Energy Metabolism, Springer.","DOI":"10.1007\/978-1-4939-1059-5"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0197-0186(93)90064-C","article-title":"Direct demonstration by [13C]NMR spectroscopy that glutamine from astrocytes is a precursor for GABA synthesis in neurons","volume":"22","author":"Sonnewald","year":"1993","journal-title":"Neurochem. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1007\/s11064-022-03771-1","article-title":"Glial Glutamine Homeostasis in Health and Disease","volume":"48","author":"Andersen","year":"2023","journal-title":"Neurochem. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1007\/s11064-016-2159-7","article-title":"Citrate, a Ubiquitous Key Metabolite with Regulatory Function in the CNS","volume":"42","author":"Westergaard","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"450","DOI":"10.2174\/1567205011666140505111354","article-title":"Early detection of cerebral glucose uptake changes in the 5XFAD mouse","volume":"11","author":"Macdonald","year":"2014","journal-title":"Curr. Alzheimer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1186\/s12974-021-02244-6","article-title":"Hippocampal glucose uptake as a surrogate of metabolic change of microglia in Alzheimer\u2019s disease","volume":"18","author":"Choi","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S1474-4422(18)30028-0","article-title":"Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer\u2019s disease: A longitudinal study","volume":"17","author":"Gordon","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s00259-014-2919-z","article-title":"Cortical hypermetabolism in MCI subjects: A compensatory mechanism?","volume":"42","author":"Ashraf","year":"2015","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"eabe5640","DOI":"10.1126\/scitranslmed.abe5640","article-title":"Microglial activation states drive glucose uptake and FDG-PET alterations in neurodegenerative diseases","volume":"13","author":"Xiang","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"E4502","DOI":"10.1073\/pnas.1317918110","article-title":"Regional variability of imaging biomarkers in autosomal dominant Alzheimer\u2019s disease","volume":"110","author":"Benzinger","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1038\/jcbfm.2011.84","article-title":"Labeled acetate as a marker of astrocytic metabolism","volume":"31","author":"Wyss","year":"2011","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/s41419-021-04237-y","article-title":"Hippocampal disruptions of synaptic and astrocyte metabolism are primary events of early amyloid pathology in the 5xFAD mouse model of Alzheimer\u2019s disease","volume":"12","author":"Andersen","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1002\/jnr.24075","article-title":"Astrocyte dysfunction in Alzheimer disease","volume":"95","author":"Acosta","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.cell.2015.12.056","article-title":"The Cellular Phase of Alzheimer\u2019s Disease","volume":"164","author":"Karran","year":"2016","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.molmed.2018.11.006","article-title":"Astrocyte Biomarkers in Alzheimer\u2019s Disease","volume":"25","author":"Carter","year":"2019","journal-title":"Trends Mol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1007\/s00018-019-03111-7","article-title":"Astrocyte alterations in neurodegenerative pathologies and their modeling in human induced pluripotent stem cell platforms","volume":"76","author":"Oksanen","year":"2019","journal-title":"Cell Mol. Life Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"423.e1","DOI":"10.1016\/j.neurobiolaging.2010.09.018","article-title":"Reactive astrocytes give neurons less support: Implications for Alzheimer\u2019s disease","volume":"33","author":"Steele","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.biocel.2016.12.015","article-title":"Fats for thoughts: An update on brain fatty acid metabolism","volume":"84","author":"Romano","year":"2017","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1111\/epi.13833","article-title":"Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium-chain triglyceride ketogenic diet","volume":"58","author":"Khabbush","year":"2017","journal-title":"Epilepsia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"472459","DOI":"10.1155\/2014\/472459","article-title":"Fatty Acids in Energy Metabolism of the Central Nervous System","volume":"2014","author":"Panov","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"101001","DOI":"10.1016\/j.arr.2019.101001","article-title":"Medium Chain Triglycerides induce mild ketosis and may improve cognition in Alzheimer\u2019s disease. A systematic review and meta-analysis of human studies","volume":"58","author":"Avgerinos","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0006-8993(79)90071-4","article-title":"Fine structural localization of glutamine synthetase in astrocytes of rat brain","volume":"161","author":"Norenberg","year":"1979","journal-title":"Brain Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1002\/jnr.24038","article-title":"Specificity of exogenous acetate and glutamate as astrocyte substrates examined in acute brain slices from female mice using methionine sulfoximine (MSO) to inhibit glutamine synthesis","volume":"95","author":"Andersen","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/978-3-319-45096-4_8","article-title":"The Glutamine Transporters and Their Role in the Glutamate\/GABA-Glutamine Cycle","volume":"13","author":"Leke","year":"2016","journal-title":"Adv. Neurobiol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Hertz, L. (2013). The Glutamate-Glutamine (GABA) Cycle: Importance of Late Postnatal Development and Potential Reciprocal Interactions between Biosynthesis and Degradation. Front. Endocrinol., 4.","DOI":"10.3389\/fendo.2013.00059"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6807","DOI":"10.1038\/ncomms7807","article-title":"Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism","volume":"6","author":"Lundgaard","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.molmet.2020.01.002","article-title":"A Neural basis for Octanoic acid regulation of energy balance","volume":"34","author":"Haynes","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1016\/j.stemcr.2017.10.016","article-title":"PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer\u2019s Disease","volume":"9","author":"Oksanen","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5702","DOI":"10.1038\/s41380-021-01068-3","article-title":"Brain cells derived from Alzheimer\u2019s disease patients have multiple specific innate abnormalities in energy metabolism","volume":"26","author":"Ryu","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13024-025-00864-7","article-title":"Mutations in PSEN1 predispose inflammation in an astrocyte model of familial Alzheimer\u2019s disease through disrupted regulated intramembrane proteolysis","volume":"20","author":"Ziff","year":"2025","journal-title":"Mol. Neurodegener."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1002\/glia.23534","article-title":"PPAR\u03b2\/\u03b4-agonist GW0742 ameliorates dysfunction in fatty acid oxidation in PSEN1\u0394E9 astrocytes","volume":"67","author":"Konttinen","year":"2019","journal-title":"Glia"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"114979","DOI":"10.1016\/j.expneurol.2024.114979","article-title":"Reactive astrocytes generated from human iPSC are pro-inflammatory and display altered metabolism","volume":"382","author":"McComish","year":"2024","journal-title":"Exp. Neurol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Afridi, R., Kim, J.-H., Rahman, M.H., and Suk, K. (2020). Metabolic Regulation of Glial Phenotypes: Implications in Neuron\u2013Glia Interactions and Neurological Disorders. Front. Cell. 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