2021
Astrocytic lipid metabolism determines susceptibility to diet-induced obesity
Varela L, Kim JG, Fernández-Tussy P, Aryal B, Liu ZW, Fernández-Hernando C, Horvath TL. Astrocytic lipid metabolism determines susceptibility to diet-induced obesity. Science Advances 2021, 7: eabj2814. PMID: 34890239, PMCID: PMC11323787, DOI: 10.1126/sciadv.abj2814.Peer-Reviewed Original ResearchDiet-induced obesityHypothalamic astrocytesPeroxisome proliferator-activated receptor gammaHypothalamic neuronal circuitsProliferator-activated receptor gammaControl of feedingFatty acid homeostasisSystemic glucoseMetabolic milieuGlucose homeostasisBody weightReceptor gammaSynaptic plasticityNeuronal circuitsNutrient sensingLipid metabolismCellular adaptationObesityAstrocytesAcid homeostasisUnidentified roleFA metabolismEnergy metabolismElevated susceptibilityAvailability of FAHunger-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 crucialFeedingObesityGABAExcitabilityChemogenetics
2017
(S)Pot on Mitochondria: Cannabinoids Disrupt Cellular Respiration to Limit Neuronal Activity
Harkany T, Horvath TL. (S)Pot on Mitochondria: Cannabinoids Disrupt Cellular Respiration to Limit Neuronal Activity. Cell Metabolism 2017, 25: 8-10. PMID: 28076767, DOI: 10.1016/j.cmet.2016.12.020.Peer-Reviewed Original Research
2016
Role of mitochondrial uncoupling protein-2 (UCP2) in higher brain functions, neuronal plasticity and network oscillation
Hermes G, Nagy D, Waterson M, Zsarnovszky A, Varela L, Hajos M, Horvath TL. Role of mitochondrial uncoupling protein-2 (UCP2) in higher brain functions, neuronal plasticity and network oscillation. Molecular Metabolism 2016, 5: 415-421. PMID: 27257601, PMCID: PMC4877662, DOI: 10.1016/j.molmet.2016.04.002.Peer-Reviewed Original ResearchMouse modelSynaptic plasticityMental illnessUCP2 knockout miceNMDA receptor blockadeHigher brain regionsKO mouse modelMajor psychiatric illnessProtein 2 expressionHigher brain functionsReceptor blockadePsychiatric illnessNeuronal plasticityKnockout miceNeural transmissionCellular resilienceCortical activityBrain regionsProfound disorderBrain functionMitochondrial impairmentIllnessNetwork oscillationsMitochondrial functionProtein 2The 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
Role of Synaptic Plasticity and EphA5-EphrinA5 Interaction Within the Ventromedial Hypothalamus in Response to Recurrent Hypoglycemia
Szepietowska B, Horvath TL, Sherwin RS. Role of Synaptic Plasticity and EphA5-EphrinA5 Interaction Within the Ventromedial Hypothalamus in Response to Recurrent Hypoglycemia. Diabetes 2014, 63: 1140-1147. PMID: 24222347, PMCID: PMC3931406, DOI: 10.2337/db13-1259.Peer-Reviewed Original ResearchConceptsRecurrent hypoglycemiaVentromedial hypothalamusEphA5 receptorNondiabetic ratsCounterregulatory responsesSynaptic plasticityAntecedent recurrent hypoglycemiaCounterregulatory hormone releaseDefective glucose counterregulationExpression of ephrinA5Counterregulatory hormone responsesIntensive insulin treatmentInsulin-induced hypoglycemiaHyperinsulinemic-hypoglycemic clamp studyGlucose infusion rateHypoglycemic clamp studiesGlucose counterregulationSynaptic coverageHypoglycemic stimulusGlucagon secretionGlucagon releaseAcute hypoglycemiaInsulin treatmentHormone releaseInfusion rate
2013
Hypothalamic control of energy balance: insights into the role of synaptic plasticity
Dietrich MO, Horvath TL. Hypothalamic control of energy balance: insights into the role of synaptic plasticity. Trends In Neurosciences 2013, 36: 65-73. PMID: 23318157, DOI: 10.1016/j.tins.2012.12.005.Peer-Reviewed Original ResearchConceptsWhole-body energy metabolismRegion-specific expressionGenetic toolsPeripheral tissue functionsMetabolism regulationMetabolic hormone receptorsEnergy metabolismTissue functionMetabolic eventsRole of neuronsHormone receptorsRegulationGlial cellsHypothalamic controlSynaptic plasticityCentral regulationNeuronal circuitsBrain circuitsEnormous leapPlasticitySurprising findingRoleExpressionMetabolismDynamic process
2011
Synaptic Plasticity of Feeding Circuits: Hormones and Hysteresis
Dietrich MO, Horvath TL. Synaptic Plasticity of Feeding Circuits: Hormones and Hysteresis. Cell 2011, 146: 863-865. PMID: 21925311, DOI: 10.1016/j.cell.2011.08.031.Peer-Reviewed Original Research
2010
Agrp Neurons Mediate Sirt1's Action on the Melanocortin System and Energy Balance: Roles for Sirt1 in Neuronal Firing and Synaptic Plasticity
Dietrich MO, Antunes C, Geliang G, Liu ZW, Borok E, Nie Y, Xu AW, Souza DO, Gao Q, Diano S, Gao XB, Horvath TL. Agrp Neurons Mediate Sirt1's Action on the Melanocortin System and Energy Balance: Roles for Sirt1 in Neuronal Firing and Synaptic Plasticity. Journal Of Neuroscience 2010, 30: 11815-11825. PMID: 20810901, PMCID: PMC2965459, DOI: 10.1523/jneurosci.2234-10.2010.Peer-Reviewed Original ResearchConceptsFood intakeMelanocortin systemAgRP neuronal activityAnorexigenic POMC neuronsHypothalamic melanocortin systemAction of SIRT1Negative energy balanceAgRP neuronsPOMC neuronsCre-lox technologyInhibitory toneMC4R antagonistFat massLean massSynaptic inputsNeuronal activityNeuronal firingAdult miceBody weightSIRT1 inhibitorSynaptic plasticityCalorie restrictionMelanocortin receptorsSIRT1 activityBody metabolism
2009
Estrogens Regulate Posttranslational Modification of Neural Cell Adhesion Molecule during the Estrogen-Induced Gonadotropin Surge
Tan O, Fadiel A, Chang A, Demir N, Jeffrey R, Horvath T, Garcia-Segura LM, Naftolin F. Estrogens Regulate Posttranslational Modification of Neural Cell Adhesion Molecule during the Estrogen-Induced Gonadotropin Surge. Endocrinology 2009, 150: 2783-2790. PMID: 19282389, DOI: 10.1210/en.2008-0927.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEstradiolEstrogensEstrous CycleFemaleGonadotropinsMiceMice, Inbred C57BLMidline Thalamic NucleiModels, AnimalNeural Cell Adhesion Molecule L1Neural Cell Adhesion MoleculesNeuronal PlasticityProtein IsoformsProtein Processing, Post-TranslationalRNA, MessengerSialic AcidsSialyltransferasesSynapsesConceptsNeural cell adhesion moleculePeriventricular areaIR-PSAPerineural spacePSA-NCAMCell adhesion moleculeAdhesion moleculesPSA-NCAM stainingExtent of stainingSialyltransferase mRNA levelsGonadotropin surgeNCAM stainingPreovulatory gonadotropinSynaptic plasticityProestrous afternoonEstrogenWestern blotProestrusIndividual neuronsRT-PCRMetestrusMRNA levelsHypothalamus tissueStainingSialyltransferase mRNA
2008
Exercise-Induced Synaptogenesis in the Hippocampus Is Dependent on UCP2-Regulated Mitochondrial Adaptation
Dietrich MO, Andrews ZB, Horvath TL. Exercise-Induced Synaptogenesis in the Hippocampus Is Dependent on UCP2-Regulated Mitochondrial Adaptation. Journal Of Neuroscience 2008, 28: 10766-10771. PMID: 18923051, PMCID: PMC3865437, DOI: 10.1523/jneurosci.2744-08.2008.Peer-Reviewed Original ResearchConceptsSynaptic plasticityVoluntary exerciseEssential organellesUCP2 functionProtein-2 mRNA expressionDendritic spine synapsesBioenergetic adaptationMitochondrial metabolismMitochondrial oxygen consumptionMitochondrial numberEnergetic needsMitochondrial adaptationsMitochondrial mechanismsExercise inducesDentate gyrusStratum radiatumSpine synapsesCA1 regionGlial morphologyHippocampal formationNeuronal activityGranule cellsAction potentialsNeuronal morphologyMRNA expressionUCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals
Andrews ZB, Liu ZW, Walllingford N, Erion DM, Borok E, Friedman JM, Tschöp MH, Shanabrough M, Cline G, Shulman GI, Coppola A, Gao XB, Horvath TL, Diano S. UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals. Nature 2008, 454: 846-851. PMID: 18668043, PMCID: PMC4101536, DOI: 10.1038/nature07181.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsCarnitine O-PalmitoyltransferaseFatty AcidsFeeding BehaviorGene Expression RegulationGhrelinHypothalamusIon ChannelsMembrane Potential, MitochondrialMiceMitochondriaMitochondrial ProteinsNeuronsNeuropeptide YPhosphorylationReactive Oxygen SpeciesSynapsesUncoupling Protein 2ConceptsNPY/AgRP neuronsAgRP neuronsNeuronal activityCo-express neuropeptide YGut-derived hormone ghrelinAgRP neuronal activityArcuate nucleus neuronsFatty acid oxidation pathwayHypothalamic mitochondrial respirationG protein-coupled receptorsGhrelin actionNeuropeptide YNucleus neuronsHormone ghrelinFood intakeGhrelinFree radicalsSynaptic plasticityNeuronal functionIntracellular mechanismsNeuronsMitochondrial mechanismsProtein 2Mitochondrial proliferationRobust changes
2007
Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons
Rao Y, Liu ZW, Borok E, Rabenstein RL, Shanabrough M, Lu M, Picciotto MR, Horvath TL, Gao XB. Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons. Journal Of Clinical Investigation 2007, 117: 4022-4033. PMID: 18060037, PMCID: PMC2104495, DOI: 10.1172/jci32829.Peer-Reviewed Original ResearchConceptsHypocretin/orexin neuronsLong-term potentiationOrexin neuronsGlutamatergic synapsesSynaptic plasticitySleep lossExperience-dependent synaptic plasticityDopamine D1 receptorsChronic sleep lossSleep-wake regulationModafinil treatmentLateral hypothalamusD1 receptorsSimilar potentiationBrain slicesNeuronal activityNeuronal circuitryDopamine systemNervous systemSynaptic strengthNeuronsPathological conditionsGentle handlingMiceWakefulnessEstrogen-Induced Hypothalamic Synaptic Plasticity and Pituitary Sensitization in the Control of the Estrogen-Induced Gonadotrophin Surge
Naftolin F, Garcia-Segura LM, Horvath TL, Zsarnovszky A, Demir N, Fadiel A, Leranth C, Vondracek-Klepper S, Lewis C, Chang A, Parducz A. Estrogen-Induced Hypothalamic Synaptic Plasticity and Pituitary Sensitization in the Control of the Estrogen-Induced Gonadotrophin Surge. Reproductive Sciences 2007, 14: 101-116. PMID: 17636222, DOI: 10.1177/1933719107301059.Peer-Reviewed Original ResearchConceptsGnRH secretionPituitary gonadotrophsGonadotrophin surgeSynaptic plasticityInsulinlike growth factor 1Triggering of ovulationOvarian estrogen secretionGrowth factor-1Neural cell adhesion moleculePituitary sensitizationGnRH cellsGnRH neuronsEstrogen secretionHypothalamic neuronsGonadal functionCell adhesion moleculeSex steroidsSpecific immunoneutralizationOvarian cycleGonadotrophsAdhesion moleculesEstrogenMaximal sensitizationSecretionFactor 1
2006
Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals
Gao Q, Mezei G, Nie Y, Rao Y, Choi CS, Bechmann I, Leranth C, Toran-Allerand D, Priest CA, Roberts JL, Gao XB, Mobbs C, Shulman GI, Diano S, Horvath TL. Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Nature Medicine 2006, 13: 89-94. PMID: 17195839, DOI: 10.1038/nm1525.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnorexiaArcuate Nucleus of HypothalamusBody WeightEstradiolEstrogen Receptor alphaExcitatory Postsynaptic PotentialsFemaleInjections, IntraventricularLeptinMaleMelanocortinsMiceMice, Inbred C57BLMice, KnockoutMice, ObeseMicroscopy, ElectronNeuronsObesityOvariectomyPro-OpiomelanocortinRatsRats, Sprague-DawleySignal TransductionSTAT3 Transcription FactorConceptsArcuate nucleusFood intakeLeptin receptor-deficient miceGonadal steroid estradiolRearrangement of synapsesReceptor-deficient miceBody weight regulationBody weight gainWild-type ratsPOMC neuronsLeptin effectsExcitatory inputsMetabolic hormonesLeptin receptorObese animalsSteroids estradiolWeight regulationBody weightSynaptic plasticityWeight gainRobust increaseInput organizationSTAT3 activationEnergy expenditureAdipositySynaptic Plasticity in Energy Balance Regulation
Horvath TL. Synaptic Plasticity in Energy Balance Regulation. Obesity 2006, 14: 228s-233s. PMID: 17021372, DOI: 10.1038/oby.2006.314.Peer-Reviewed Original ResearchConceptsOb/ob miceNumber of excitatoryNeuropeptide YSynaptic plasticityPOMC neuronsOb miceFood intakeBehavioral effectsLeptin receptor-deficient miceRearrangement of synapsesLeptin-deficient miceReceptor-deficient miceHypothalamic arcuate nucleusOb/obEnergy balance regulationWild-type miceInfluences brain functionObserved synaptic plasticityWild-type animalsProopiomelanocortin neuronsAnorexigenic hormonesOrexigenic hormonePost-synaptic densityGlutamate inputsExtrahypothalamic sitesGhrelin controls hippocampal spine synapse density and memory performance
Diano S, Farr SA, Benoit SC, McNay EC, da Silva I, Horvath B, Gaskin FS, Nonaka N, Jaeger LB, Banks WA, Morley JE, Pinto S, Sherwin RS, Xu L, Yamada KA, Sleeman MW, Tschöp MH, Horvath TL. Ghrelin controls hippocampal spine synapse density and memory performance. Nature Neuroscience 2006, 9: 381-388. PMID: 16491079, DOI: 10.1038/nn1656.Peer-Reviewed Original ResearchConceptsHippocampal spine synapse densitySpine synapse densitySpine synapse formationGrowth hormone releaseNovel therapeutic strategiesLong-term potentiationHigher brain functionsEnhanced spatial learningGut hormonesGhrelin administrationHypothalamic actionSynapse densitySpine synapsesCA1 regionHormone releaseNeuropeptide ghrelinGhrelin bindingHippocampal formationTherapeutic strategiesMelanocortin systemGhrelinBrain areasMetabolic controlSynaptic changesSynaptic plasticitySynaptic plasticity mediating leptin's effect on metabolism
Horvath TL. Synaptic plasticity mediating leptin's effect on metabolism. Progress In Brain Research 2006, 153: 47-55. PMID: 16876567, DOI: 10.1016/s0079-6123(06)53002-x.Peer-Reviewed Original ResearchConceptsPrimate hypothalamusSynaptic plasticityEnergy homeostasisShort-term fastingLeptin effectsHypothalamic regulationSynaptic inputsNeuromodulator systemsPeptidergic circuitsHypothalamusNonhuman primatesPathological conditionsBasic wiringMetabolic statePhysiological regulationHomeostasisMetabolic circuitsRodent speciesRatsFastingMicePlasticityResponse
2005
The hardship of obesity: a soft-wired hypothalamus
Horvath TL. The hardship of obesity: a soft-wired hypothalamus. Nature Neuroscience 2005, 8: 561-565. PMID: 15856063, DOI: 10.1038/nn1453.Peer-Reviewed Original ResearchConceptsFood intakeMetabolic disordersEnergy expenditureHumoral responseHomeostatic feedback loopSynaptic plasticityBrain circuitryObesityCentral therapyMetabolic phenotypeCellular mechanismsBrain anatomyMetabolic cuesIntakeDisordersCurrent knowledgeMajor advancesHeavy tollMorbidityDiabetesHypothalamusTherapyCNSMortalityMetabolic processes
2004
The floating blueprint of hypothalamic feeding circuits
Horvath TL, Diano S. The floating blueprint of hypothalamic feeding circuits. Nature Reviews Neuroscience 2004, 5: 662-667. PMID: 15263896, DOI: 10.1038/nrn1479.Peer-Reviewed Original ResearchConceptsHypothalamic feeding circuitsNew therapeutic avenuesMetabolic parametersFood intakeMetabolic disordersSynaptic plasticityTherapeutic avenuesLesion studiesGenetic findingsEnergy expenditureEarlier lesion studiesCircuit changesHypothalamusImportant regulatorUnexpected findingMetabolism regulationFeeding circuitFindingsIntakeAppetite