{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:12:52Z","timestamp":1788415972947,"version":"build-2803163510"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Syst. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Mild cognitive impairment (MCI) represents a prodromal stage of Alzheimer\u2019s disease (AD), but the metabolic mechanisms underlying early neuronal dysfunction remain incompletely understood. GABAergic neurons, which maintain excitatory\u2013inhibitory balance and network stability, exhibit early vulnerability during neurodegeneration, although the metabolic alterations associated with their dysfunction remain poorly characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a context-specific genome-scale metabolic model (GEM) of human GABAergic neurons across the MCI\u2013AD continuum using deconvolved hippocampal transcriptomic data. By integrating transcriptomic deconvolution with constraint-based modeling, including flux balance analysis (FBA) and flux variability analysis (FVA), we inferred disease-stage-associated metabolic alterations under Control, early MCI (E-MCI), advanced MCI (A-MCI), and AD conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our analyses suggest progressive remodeling of energy metabolism, the glutamate\u2013glutamine\u2013GABA cycle, redox homeostasis, lipid metabolism, and neuron\u2013astrocyte metabolic interactions. FVA identified reaction-specific changes in feasible flux ranges, indicating remodeling of the feasible metabolic solution space rather than a uniform contraction across pathways. These predicted metabolic alterations were accompanied by transcriptional changes in GABAergic markers and showed qualitative agreement with independent metabolomic observations, supporting their biological plausibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Overall, this work provides a systems-level computational framework linking transcriptomic alterations with predicted metabolic remodeling in GABAergic neurons and generates experimentally testable hypotheses regarding metabolic dysfunction during progression from MCI to AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fsysb.2026.1897648","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:17:04Z","timestamp":1788412624000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative genome-scale metabolic model of GABAergic neurons reveals metabolic signatures across the mild cognitive impairment \u2013 Alzheimer disease continuum"],"prefix":"10.3389","volume":"6","author":[{"given":"Andrea","family":"Angarita-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Departamento de Nutrici\u00f3n y Bioqu\u00edmica, Facultad de Ciencias, Pontificia Universidad Javeriana","place":["Bogot\u00e1, Colombia"]},{"name":"Laboratorio de Bioinform\u00e1tica y Biolog\u00eda de Sistemas, Universidad Nacional de Colombia Bogot\u00e1","place":["Bogot\u00e1, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan H.","family":"Largo-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Departamento de Nutrici\u00f3n y Bioqu\u00edmica, Facultad de Ciencias, Pontificia Universidad Javeriana","place":["Bogot\u00e1, Colombia"]},{"name":"Laboratorio de Bioinform\u00e1tica y Biolog\u00eda de Sistemas, Universidad Nacional de Colombia Bogot\u00e1","place":["Bogot\u00e1, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juli\u00e1n","family":"P\u00e9rez-Mej\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Nutrici\u00f3n y Bioqu\u00edmica, Facultad de Ciencias, Pontificia Universidad Javeriana","place":["Bogot\u00e1, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Balcazar","sequence":"additional","affiliation":[{"name":"Departamento de Nutrici\u00f3n y Bioqu\u00edmica, Facultad de Ciencias, Pontificia Universidad Javeriana","place":["Bogot\u00e1, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana","family":"Vargas-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Departamento de Nutrici\u00f3n y Bioqu\u00edmica, Facultad de Ciencias, Pontificia Universidad Javeriana","place":["Bogot\u00e1, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason A.","family":"Papin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Virginia","place":["Charlottesville, VA, United States"]},{"name":"Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia","place":["Charlottesville, VA, United States"]},{"name":"Department of Biochemistry & Molecular Genetics, University of Virginia","place":["Charlottesville, VA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Pinz\u00f3n","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioinform\u00e1tica y Biolog\u00eda de Sistemas, Universidad Nacional de Colombia Bogot\u00e1","place":["Bogot\u00e1, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneth","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Departamento de Nutrici\u00f3n y Bioqu\u00edmica, Facultad de Ciencias, Pontificia Universidad Javeriana","place":["Bogot\u00e1, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1007\/s11910-011-0203-1","article-title":"Mild cognitive impairment in Parkinson\u2019s disease","volume":"11","author":"Aarsland","year":"2011","journal-title":"Curr. Neurology Neurosci. Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1159\/000113014","article-title":"Predicting rapid clinical progression in amnestic mild cognitive impairment","author":"Ahmed","year":"2008"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e70029","DOI":"10.1111\/jnc.70029","article-title":"The Glutamate\/GABA-Glutamine cycle: insights, updates, and advances","volume":"169","author":"Andersen","year":"2025","journal-title":"J. Neurochem."},{"key":"B4","doi-asserted-by":"publisher","first-page":"365","DOI":"10.3390\/ijms25010365","article-title":"Control theory and systems biology: potential applications in neurodegeneration and search for therapeutic targets","volume":"25","author":"Angarita-Rodr\u00edguez","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1816121","DOI":"10.3389\/fbinf.2026.1816121","article-title":"Transcriptome-informed metabolic modeling reveals astrocyte-specific vulnerabilities in mild cognitive impairment and Alzheimer\u2019s disease progression","volume":"6","author":"Angarita-Rodr\u00edguez","year":"2026","journal-title":"Front. Bioinforma."},{"key":"B6","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1007\/s10571-026-01691-0","article-title":"Immunometabolism reframes Alzheimer\u2019s disease: from systemic dysmetabolism to glial rewiring","volume":"46","author":"Bach","year":"2026","journal-title":"Cell. Mol. Neurobiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1111\/j.1471-4159.2006.03913.x","article-title":"The glutamate\/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer","volume":"98","author":"Bak","year":"2006","journal-title":"J. Neurochem."},{"key":"B8","doi-asserted-by":"publisher","first-page":"100138","DOI":"10.1016\/j.xcrm.2020.100138","article-title":"Metabolic network analysis reveals altered bile acid synthesis and metabolism in Alzheimer\u2019s disease","volume":"1","author":"Baloni","year":"2020","journal-title":"Cell Rep. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.coph.2021.06.012","article-title":"Systems modeling of metabolic dysregulation in neurodegenerative diseases","volume":"60","author":"Baloni","year":"2021","journal-title":"Curr. Opin. Pharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/2470547017720459","article-title":"Characterization of GABAergic marker expression in the chronic unpredictable stress model of depression","volume":"1","author":"Banasr","year":"2017","journal-title":"Chronic Stress"},{"key":"B11","doi-asserted-by":"publisher","first-page":"E2725","DOI":"10.1073\/pnas.1504393112","article-title":"Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro","volume":"112","author":"Bardy","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e1000082","DOI":"10.1371\/journal.pcbi.1000082","article-title":"Context-specific metabolic networks are consistent with experiments","volume":"4","author":"Becker","year":"2008","journal-title":"PLoS Comput. Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1002\/alz.12088","article-title":"GABAergic dysfunction in excitatory and inhibitory (E\/I) imbalance drives the pathogenesis of Alzheimer\u2019s disease","volume":"16","author":"Bi","year":"2020","journal-title":"Alzheimer\u2019s Dementia"},{"key":"B14","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.jchemneu.2011.06.007","article-title":"Microarray analyses of laser-captured hippocampus reveal distinct gray and white matter signatures associated with incipient Alzheimer\u2019s disease","volume":"42","author":"Blalock","year":"2011","journal-title":"J. Chem. Neuroanat."},{"key":"B15","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/nrg3643","article-title":"Constraint-based models predict metabolic and associated cellular functions","volume":"15","author":"Bordbar","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"B16","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/nbt.4072","article-title":"Recon3D enables a three-dimensional view of gene variation in human metabolism","volume":"36","author":"Brunk","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1101\/gr.1926504","article-title":"Flux coupling analysis of genome-scale metabolic network reconstructions","volume":"4","author":"Burgard","year":"2004","journal-title":"Genome Res."},{"key":"B18","doi-asserted-by":"publisher","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":"B19","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/j.cger.2013.07.009","article-title":"Risk factors for the progression of mild cognitive impairment to dementia","volume":"29","author":"Campbell","year":"2013","journal-title":"Clin. Geriatric Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"6929732","DOI":"10.1155\/2018\/6929732","article-title":"Risk factors for the progression of mild cognitive impairment in different types of neurodegenerative disorders","volume":"2018","author":"Chen","year":"2018","journal-title":"Behav. Neurol."},{"key":"B21","unstructured":"The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure the JNC 7 report\n          \n          \n            \n              Chobanian\n              A. V.\n            \n            \n              Bakris\n              G. L.\n            \n            \n              Black\n              H. R.\n            \n            \n              Cushman\n              W. C.\n            \n            \n              Green\n              L. A.\n            \n            \n              Izzo\n              J. L.\n            \n          \n          \n          2004"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-1-4614-7320-6_100691-1","article-title":"Neuron-glial interactions","author":"De Pitt\u00e0","year":"2020","journal-title":"Encycl. Comput. Neurosci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1212\/01.wnl.0000171450.97464.49","article-title":"Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD","volume":"65","author":"Dickerson","year":"2005","journal-title":"Neurology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1073\/pnas.0610772104","article-title":"Global reconstruction of the human metabolic network based on genomic and bibliomic data","volume":"104","author":"Duarte","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B25","first-page":"1","volume-title":"Multi-Omic Data Integration Enables Discovery of Hidden Biological Regularities","author":"Ebrahim","year":"2016"},{"key":"B26","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.jneumeth.2010.04.030","article-title":"Addition of glutamate to serum-free culture promotes recovery of electrical activity in adult hippocampal neurons in vitro","volume":"190","author":"Edwards","year":"2010","journal-title":"J. Neurosci. Methods"},{"key":"B27","doi-asserted-by":"publisher","first-page":"743","DOI":"10.3238\/arztebl.2011.0743","article-title":"Mild cognitive impairment and dementia","volume":"108","author":"Etgen","year":"2011","journal-title":"Dtsch. Arztebl Int."},{"key":"B28","doi-asserted-by":"publisher","first-page":"738686","DOI":"10.3389\/fnagi.2021.738686","article-title":"Relieving cellular energy stress in aging, neurodegenerative, and metabolic diseases, SIRT1 as a therapeutic and promising node","volume":"13","author":"Fang","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.mib.2010.03.003","article-title":"The biomass objective function","volume":"13","author":"Feist","year":"2010","journal-title":"Curr. Opin. Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pcbi.1009550","article-title":"GPRuler: metabolic gene-protein-reaction rules automatic reconstruction","volume":"17","author":"Filippo","year":"2021","journal-title":"PLoS Comput. Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1220122","DOI":"10.3389\/fnins.2023.1220122","article-title":"Decreased GABA levels of the anterior and posterior cingulate cortex are associated with executive dysfunction in mild cognitive impairment","volume":"17","author":"Fu","year":"2023","journal-title":"Front. Neurosci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/jdn.10242","article-title":"GABAergic neurons maturation is regulated by a delicate network","volume":"83","author":"Gao","year":"2023","journal-title":"Int. J. Dev. Neurosci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"4833","DOI":"10.1038\/s41598-018-23155-2","article-title":"Dynamic metabolic patterns tracking neurodegeneration and gliosis following 26S proteasome dysfunction in mouse forebrain neurons","volume":"8","author":"Geiszler","year":"2018","journal-title":"Sci. Rep."},{"key":"B34","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/s13059-019-1730-3","article-title":"Current status and applications of genome-scale metabolic models","volume":"20","author":"Gu","year":"2019","journal-title":"Genome Biol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/msb.2011.28","article-title":"RNA sequencing reveals two major classes of gene expression levels in metazoan cells","volume":"7","author":"Hebenstreit","year":"2011","journal-title":"Mol. Syst. Biol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41596-018-0098-2","article-title":"Creation and analysis of biochemicals constraint-based models using the COBRA toolbox","volume":"3","author":"Heirendt","year":"2011"},{"key":"B37","first-page":"639","article-title":"Creation and analysis of biochemical constraint-based models using the COBRA toolbox","volume":"3","author":"Heirendt","year":"2019"},{"key":"B38","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s13041-021-00746-1","article-title":"GABAergic neuron-specific whole-brain transduction by AAV-PHP.B incorporated with a new GAD65 promoter","volume":"14","author":"Hoshino","year":"2021","journal-title":"Mol. Brain"},{"key":"B73","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA research framework: toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"B39","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1186\/s12859-021-04186-5","article-title":"CDSeqR: fast complete deconvolution for gene expression data from bulk tissues","volume":"22","author":"Kang","year":"2021","journal-title":"BMC Bioinforma."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cells11162486","article-title":"Review of current human genome-scale metabolic models for brain cancer and neurodegenerative diseases","volume":"11","author":"Kishk","year":"2022","journal-title":"Cells"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pcbi.1005457","article-title":"Transcriptomics technologies","volume":"13","author":"Lowe","year":"2017","journal-title":"PLoS Comput. Biol."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1101\/2025.06.15.659811","article-title":"Proteomic and metabolic profiling reveals APOE4 -dependent shifts in whole brain, neuronal, and astrocytic mitochondrial function and glycolysis","author":"Lysaker","year":"2025"},{"key":"B43","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1002\/biot.201200291","article-title":"Basic concepts and principles of stoichiometric modeling of metabolic networks","volume":"8","author":"Maarleveld","year":"2013","journal-title":"Biotechnol. J."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e70084","DOI":"10.1111\/jnc.70084","article-title":"Neural metabolic networks: key elements of healthy brain function","volume":"169","author":"Madrer","year":"2025","journal-title":"J. Neurochem."},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.64898\/2025.12.05.25341709","article-title":"A seven-year longitudinal study of the Alzheimer\u2019s disease blood metabolome","author":"Marella","year":"2025","journal-title":"MedRxiv Peprint"},{"key":"B46","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/s41467-019-13668-3","article-title":"Mitochondrial TCA cycle metabolites control physiology and disease","volume":"11","author":"Mart\u00ednez-Reyes","year":"2020","journal-title":"Nat. Commun."},{"key":"B47","doi-asserted-by":"publisher","first-page":"103994","DOI":"10.1016\/j.compbiomed.2020.103994","article-title":"Genome-scale metabolic modelling predicts biomarkers and therapeutic targets for neuropsychiatric disorders","volume":"125","author":"Moolamalla","year":"2020","journal-title":"Comput. Biol. Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s00401-011-0884-1","article-title":"Mild cognitive impairment: pathology and mechanisms","volume":"123","author":"Mufson","year":"2012","journal-title":"Acta Neuropathol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1007\/s10571-025-01555-z","article-title":"Energy metabolism and brain aging: strategies to delay neuronal degeneration","volume":"45","author":"Na","year":"2025","journal-title":"Cell. Mol. Neurobiol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"67","DOI":"10.24875\/rmn.20000050","article-title":"The role of GABA neurotransmitter in the human central nervous system, physiology, and pathophysiology","volume":"22","author":"Ochoa-de la Paz","year":"2021","journal-title":"Rev. Mex. Neurocienc."},{"key":"B51","doi-asserted-by":"publisher","first-page":"e57","DOI":"10.1038\/tp.2011.55","article-title":"Metabolome in progression to Alzheimer\u2019s disease","volume":"1","author":"Ore\u0161i\u010d","year":"2011","journal-title":"Transl. Psychiatry"},{"key":"B52","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/nbt.1614","article-title":"What is flux balance analysis?","volume":"28","author":"Orth","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"B53","volume-title":"Package \u2018 exp2flux","author":"Osorio","year":"2016"},{"key":"B54","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.bbi.2018.10.009","article-title":"IL-1\u03b2 expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala","volume":"75","author":"Patel","year":"2019","journal-title":"Brain, Behav. Immun."},{"key":"B55","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1002\/gps.2535","article-title":"Neuropsychiatric symptoms in MCI subtypes: the importance of executive dysfunction","volume":"26","author":"Rosenberg","year":"2011","journal-title":"Int. J. Geriatric Psychiatry"},{"key":"B56","first-page":"805830","volume-title":"Neural PlastGABA Metabolism and Transport: Effects on Synaptic Efficacy","author":"Roth","year":"2012"},{"key":"B57","doi-asserted-by":"publisher","first-page":"670346","DOI":"10.3389\/fncel.2021.670346","article-title":"Regulation of glutamate, GABA and dopamine transporter uptake, surface mobility and expression","volume":"15","author":"Ryan","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"B58","doi-asserted-by":"publisher","first-page":"736580","DOI":"10.3389\/fnagi.2021.736580","article-title":"Functional metabolic mapping reveals highly active branched-chain amino acid metabolism in human astrocytes, which is impaired in iPSC-Derived astrocytes in Alzheimer\u2019s disease","volume":"13","author":"Salcedo","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"102","DOI":"10.3389\/fendo.2013.00102","article-title":"Astrocytic control of biosynthesis and turnover of the neurotransmitters glutamate and GABA","volume":"4","author":"Schousboe","year":"2013","journal-title":"Front. Endocrinol. Front. Endocrinol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"590","DOI":"10.18632\/aging.100486","article-title":"Plasma microRNA biomarkers for detection of mild cognitive impairment","volume":"4","author":"Sheinerman","year":"2012","journal-title":"Aging (Albany. NY)."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.3390\/cells13201714","article-title":"Brain metabolism in health and neurodegeneration: the iInterplay among neurons and astrocytes","volume":"13","author":"Shichkova","year":"2024","journal-title":"Cells"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnins.2023.1219569","article-title":"Free-choice high-fat diet consumption reduces lateral hypothalamic GABAergic activity, without disturbing neural response to sucrose drinking in mice","volume":"17","author":"Slomp","year":"2023","journal-title":"Front. Neurosci."},{"key":"B63","volume-title":"Gene Set Enrichment Analysis: A Knowledge-based Approach for Interpreting Genome-wide","author":"Subramanian","year":"2005"},{"key":"B64","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1007\/s12576-018-0622-8","article-title":"New insight into GABAergic neurons in the hypothalamic feeding regulation","volume":"68","author":"Suyama","year":"2018","journal-title":"J. Physiol. Sci."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fpls.2011.00038","article-title":"Flux-balance modeling of plant metabolism","volume":"2","author":"Sweetlove","year":"2011","journal-title":"Front. Plant Sci."},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.37","article-title":"Genome-scale metabolic networks","author":"Terzer","year":"2009"},{"key":"B67","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.neunet.2011.03.013","article-title":"A neuron-astrocyte transistor-like model for neuromorphic dressed neurons","volume":"24","author":"Valenza","year":"2011","journal-title":"Neural Netw."},{"key":"B68","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/s12064-012-0162-3","article-title":"Measurement of mRNA abundance using RNA-seq data: RPKM measure is inconsistent among samples","volume":"131","author":"Wagner","year":"2012","journal-title":"Theory Biosci."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1551741","DOI":"10.3389\/fendo.2025.1551741","article-title":"Hypothalamic GABAergic neurons: their roles in health and metabolic diseases","volume":"16","author":"Wang","year":"2025","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"B70","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/aps.2017.172","article-title":"GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia","volume":"39","author":"Xu","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"B71","doi-asserted-by":"publisher","first-page":"e14617","DOI":"10.1111\/cns.14617","article-title":"The role of glutamate and glutamine metabolism and related transporters in nerve cells","volume":"30","author":"Zhang","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"B72","doi-asserted-by":"crossref","unstructured":"iMAT: an integrative metabolic analysis tool\n          \n          3140\n          3142\n          \n            \n              Zur\n              H.\n            \n            \n              Ruppin\n              E.\n            \n            \n              Shlomi\n              T.\n            \n          \n          10.1093\/bioinformatics\/btq602\n          21081510\n          26\n          2010","DOI":"10.1093\/bioinformatics\/btq602"}],"container-title":["Frontiers in Systems Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsysb.2026.1897648\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:17:10Z","timestamp":1788412630000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsysb.2026.1897648\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":73,"alternative-id":["10.3389\/fsysb.2026.1897648"],"URL":"https:\/\/doi.org\/10.3389\/fsysb.2026.1897648","relation":{},"ISSN":["2674-0702"],"issn-type":[{"value":"2674-0702","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"article-number":"1897648"}}