2023
Neonatal loss of FGFR2 in astroglial cells affects locomotion, sociability, working memory, and glia-neuron interactions in mice
Stevens H, Scuderi S, Collica S, Tomasi S, Horvath T, Vaccarino F. Neonatal loss of FGFR2 in astroglial cells affects locomotion, sociability, working memory, and glia-neuron interactions in mice. Translational Psychiatry 2023, 13: 89. PMID: 36906620, PMCID: PMC10008554, DOI: 10.1038/s41398-023-02372-y.Peer-Reviewed Original ResearchConceptsFibroblast growth factor receptor 2Anxiety-like behaviorAttention deficit hyperactivity disorderAstroglial cellsGrowth factor receptor 2Reduced anxiety-like behaviorGlia-neuron interactionsAstroglial cell functionEarly postnatal periodFactor receptor 2Early postnatal lossPostnatal mouse brainWeeks of ageDeficit hyperactivity disorderGlial cellsGlutamine synthetase expressionBehavioral deficitsPostnatal periodReceptor 2Floxed miceHGFAP-CreMouse brainNeonatal lossPostnatal astrogliaPostnatal loss
2022
Paraventricular glia drive circuit function to control metabolism
Varela L, Horvath TL. Paraventricular glia drive circuit function to control metabolism. Cell Metabolism 2022, 34: 1424-1426. PMID: 36198288, DOI: 10.1016/j.cmet.2022.09.012.Peer-Reviewed Original Research
2021
Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward auto-activation loop in mice
Varela L, Stutz B, Song JE, Kim JG, Liu ZW, Gao XB, Horvath TL. Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward auto-activation loop in mice. Journal Of Clinical Investigation 2021, 131 PMID: 33848272, PMCID: PMC8121506, DOI: 10.1172/jci144239.Peer-Reviewed Original ResearchConceptsAgRP neuronsHypothalamic feeding circuitsInhibitory neurotransmitter GABAGhrelin administrationInhibitory toneAstrocytic responseMetabolic milieuProstaglandin E2Neurotransmitter GABANeuronal controlSynaptic plasticityGlial processesNeuronsNeural excitationMitochondrial adaptationsFood deprivationAstrocytesPerikaryaFeeding circuitRegion crucialFeedingObesityGABAExcitabilityChemogeneticsObesity-associated hyperleptinemia alters the gliovascular interface of the hypothalamus to promote hypertension
Gruber T, Pan C, Contreras RE, Wiedemann T, Morgan DA, Skowronski AA, Lefort S, De Bernardis Murat C, Le Thuc O, Legutko B, Ruiz-Ojeda FJ, de la Fuente-Fernández M, García-Villalón AL, González-Hedström D, Huber M, Szigeti-Buck K, Müller TD, Ussar S, Pfluger P, Woods SC, Ertürk A, LeDuc CA, Rahmouni K, Granado M, Horvath TL, Tschöp MH, García-Cáceres C. Obesity-associated hyperleptinemia alters the gliovascular interface of the hypothalamus to promote hypertension. Cell Metabolism 2021, 33: 1155-1170.e10. PMID: 33951475, PMCID: PMC8183500, DOI: 10.1016/j.cmet.2021.04.007.Peer-Reviewed Original ResearchConceptsBlood pressureObesity-associated increaseObesity-induced hypertensionElevated blood pressureSystemic blood pressureEndothelial growth factorHIF1α-VEGFArterial hypertensionNovel mechanistic linkSympathetic hyperactivityHemodynamic homeostasisHypothalamic astrocytesMetabolic syndromeRegion-specific lossMacrovascular systemsLeptin signalingBrain centersPathophysiological processesHypertensionGliovascular interfacePathway disruptionGrowth factorAstrocytesMechanistic linkAngiopathy
2020
GLP-1 Receptor Signaling in Astrocytes Regulates Fatty Acid Oxidation, Mitochondrial Integrity, and Function
Timper K, del Río-Martín A, Cremer AL, Bremser S, Alber J, Giavalisco P, Varela L, Heilinger C, Nolte H, Trifunovic A, Horvath TL, Kloppenburg P, Backes H, Brüning JC. GLP-1 Receptor Signaling in Astrocytes Regulates Fatty Acid Oxidation, Mitochondrial Integrity, and Function. Cell Metabolism 2020, 31: 1189-1205.e13. PMID: 32433922, PMCID: PMC7272126, DOI: 10.1016/j.cmet.2020.05.001.Peer-Reviewed Original Research
2018
Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism
García-Cáceres C, Balland E, Prevot V, Luquet S, Woods SC, Koch M, Horvath TL, Yi CX, Chowen JA, Verkhratsky A, Araque A, Bechmann I, Tschöp MH. Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism. Nature Neuroscience 2018, 22: 7-14. PMID: 30531847, DOI: 10.1038/s41593-018-0286-y.Peer-Reviewed Original ResearchConceptsControl of metabolismNon-neuronal cellsNeuronal-glial networksFunctional interactionSpecific neuronal subpopulationsEnergy metabolismHypothalamic feeding circuitsRole of astrocytesPhysiological responsesGlial-neuronal interactionsMetabolismFood-related cuesNeuronal subpopulationsSystemic metabolismFood intakeBrain controlMetabolic statusRecent advancesMicrogliaAstrocytesGeneticsTanycytesComplex setBiologyInteroceptive signals
2016
Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability
García-Cáceres C, Quarta C, Varela L, Gao Y, Gruber T, Legutko B, Jastroch M, Johansson P, Ninkovic J, Yi CX, Le Thuc O, Szigeti-Buck K, Cai W, Meyer CW, Pfluger PT, Fernandez AM, Luquet S, Woods SC, Torres-Alemán I, Kahn CR, Götz M, Horvath TL, Tschöp MH. Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability. Cell 2016, 166: 867-880. PMID: 27518562, PMCID: PMC8961449, DOI: 10.1016/j.cell.2016.07.028.Peer-Reviewed Original ResearchConceptsBlood-brain barrierSystemic glucose metabolismInsulin receptorGlucose metabolismGlucose uptakeGlial fibrillary acidic proteinBrain glucose uptakePostnatal ablationHypothalamic glucose sensingGlutamate-aspartate transporterFibrillary acidic proteinPositron emission tomographyMelanocortin neuronsKO miceGlucose levelsAstrocyte morphologyNormal responseEmission tomographyGlucose-induced activationAcidic proteinAspartate transporterCircuit connectivityInsulinGlucose availabilityMitochondrial functionThe role of astrocytes in the hypothalamic response and adaptation to metabolic signals
Chowen JA, Argente-Arizón P, Freire-Regatillo A, Frago LM, Horvath TL, Argente J. The role of astrocytes in the hypothalamic response and adaptation to metabolic signals. Progress In Neurobiology 2016, 144: 68-87. PMID: 27000556, DOI: 10.1016/j.pneurobio.2016.03.001.Peer-Reviewed Original ResearchConceptsHypothalamic responseMetabolic signalsRole of astrocytesIncidence of obesityAnorexigenic hormone leptinType 2 diabetesHypothalamic adaptationsImportant metabolic signalsDiabetes mellitusHypothalamic circuitsSecondary complicationsChronic conditionsHormone leptinGlial cellsSynaptic transmissionAdequate treatmentMetabolic diseasesSynaptic plasticityNeuroendocrine controlHomeostatic functionsNeighboring neuronsMetabolic homeostasisHormonal inputsObesityHypothalamus
2014
Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding
Kim JG, Suyama S, Koch M, Jin S, Argente-Arizon P, Argente J, Liu ZW, Zimmer MR, Jeong JK, Szigeti-Buck K, Gao Y, Garcia-Caceres C, Yi CX, Salmaso N, Vaccarino FM, Chowen J, Diano S, Dietrich MO, Tschöp MH, Horvath TL. Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding. Nature Neuroscience 2014, 17: 908-910. PMID: 24880214, PMCID: PMC4113214, DOI: 10.1038/nn.3725.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesCell CountEatingExcitatory Postsynaptic PotentialsGlial Fibrillary Acidic ProteinHypothalamusImmunohistochemistryIn Situ HybridizationLeptinMaleMelanocortinsMiceMice, KnockoutMicroscopy, ElectronNerve NetNeuronsPrimary Cell CulturePro-OpiomelanocortinPulmonary Gas ExchangeReal-Time Polymerase Chain ReactionRNA, MessengerSignal Transduction
2013
Uncovering Novel Roles of Nonneuronal Cells in Body Weight Homeostasis and Obesity
Chowen JA, Argente J, Horvath TL. Uncovering Novel Roles of Nonneuronal Cells in Body Weight Homeostasis and Obesity. Endocrinology 2013, 154: 3001-3007. PMID: 23798599, PMCID: PMC3749483, DOI: 10.1210/en.2013-1303.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesEnergy MetabolismEpendymaHomeostasisHumansHypothalamusMicrogliaObesityConceptsGlial cellsDiverse functionsNovel rolePhysiological functionsNumerous pathologiesPhysiological regulationNonneuronal cellsBody weight homeostasisCentral nervous systemSecondary complicationsWeight homeostasisCellsPathophysiological responsesSystemic metabolismMetabolic controlNervous systemVast lackPoor nutritionStructural supportNeuroendocrine researchObesityAreas of neuroscienceRecent advancesHeterogeneous classRole
2012
Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes
Fuente-Martín E, García-Cáceres C, Granado M, de Ceballos ML, Sánchez-Garrido MÁ, Sarman B, Liu ZW, Dietrich MO, Tena-Sempere M, Argente-Arizón P, Díaz F, Argente J, Horvath TL, Chowen JA. Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes. Journal Of Clinical Investigation 2012, 122: 3900-3913. PMID: 23064363, PMCID: PMC3484452, DOI: 10.1172/jci64102.Peer-Reviewed Original ResearchConceptsGlial structural proteinsPathology of obesityHypothalamic proopiomelanocortin (POMC) neuronsGlial cell activityOffspring of mothersHigh-fat dietActivity of neuronsExpression of glucoseProopiomelanocortin neuronsHypothalamic astrocytesGlial cellsBody weightSynaptic efficacyGlutamate transportersNeuronal functionCell activityLeptinGlucose uptakeMetabolic statusElectrical activityMetabolic signalsNeuronsAppetiteGlucose transporterKey regulator
2011
Differential Acute and Chronic Effects of Leptin on Hypothalamic Astrocyte Morphology and Synaptic Protein Levels
García-Cáceres C, Fuente-Martín E, Burgos-Ramos E, Granado M, Frago LM, Barrios V, Horvath T, Argente J, Chowen JA. Differential Acute and Chronic Effects of Leptin on Hypothalamic Astrocyte Morphology and Synaptic Protein Levels. Endocrinology 2011, 152: 1809-1818. PMID: 21343257, PMCID: PMC3860256, DOI: 10.1210/en.2010-1252.Peer-Reviewed Original ResearchConceptsGlial fibrillary acidic proteinChronic leptin exposureSynaptic inputsAstrocyte morphologyLeptin exposureGFAP levelsGlial structural proteinsSynaptic protein densityChronic leptin administrationAcute leptin treatmentSynaptic protein levelsAdult male ratsCentral leptin resistanceFibrillary acidic proteinLevels 1 hPossible direct effectGlial ensheathingNeonatal overnutritionGlial activationLeptin levelsLeptin administrationHypothalamic neuronsLeptin resistanceLeptin treatmentMale rats
2003
Estrogen, synaptic plasticity and hypothalamic reproductive aging
Hung AJ, Stanbury MG, Shanabrough M, Horvath TL, Garcia-Segura LM, Naftolin F. Estrogen, synaptic plasticity and hypothalamic reproductive aging. Experimental Gerontology 2003, 38: 53-59. PMID: 12543261, DOI: 10.1016/s0531-5565(02)00183-3.Peer-Reviewed Original ResearchConceptsConstant estrusReproductive agingEstrogen exposureMale ratsAnti-oxidant vitamin EEarly estrogen exposureArcuate nucleus neuronsHypothalamic arcuate nucleus neuronsConstant vaginal estrusHypothalamic failureEstradiol exposureGonadotrophin surgeOvarian estrogenArcuate nucleusConstant diestrusNucleus neuronsOvarian failureElevated estradiolPerikaryal membraneFemale ratsPerinatal periodTesticular androgensRat brainSex steroidsHormonal factors
1998
Kainate Glutamate Receptors (GluR5–7) in the Rat Arcuate Nucleus: Relationship to Tanycytes, Astrocytes, Neurons and Gonadal Steroid Receptors
Diano S, Naftolin F, Horvath T. Kainate Glutamate Receptors (GluR5–7) in the Rat Arcuate Nucleus: Relationship to Tanycytes, Astrocytes, Neurons and Gonadal Steroid Receptors. Journal Of Neuroendocrinology 1998, 10: 239-247. PMID: 9630393, DOI: 10.1046/j.1365-2826.1998.00195.x.Peer-Reviewed Original ResearchConceptsGonadal steroid receptorsKainate glutamate receptorsArcuate nucleusGlutamate receptorsKainate receptorsSteroid receptorsGlutamate actionAndrogen receptorGlial elementsMorphological synaptic plasticityNeuro-glial interactionsRat arcuate nucleusIonotropic glutamate receptorsElectron microscopic immunocytochemistrySame perikaryaGonadal steroidsExcitatory neurotransmissionSynaptic plasticityMicroscopic immunocytochemistryReceptorsNeuronsCell populationsDouble labelHormone regulationAstrocytes