2016
Bisphenol A influences oestrogen- and thyroid hormone-regulated thyroid hormone receptor expression in rat cerebellar cell culture.
Somogyi V, Horváth TL, Tóth I, Bartha T, Frenyó LV, Kiss DS, Jócsák G, Kerti A, Naftolin F, Zsarnovszky A. Bisphenol A influences oestrogen- and thyroid hormone-regulated thyroid hormone receptor expression in rat cerebellar cell culture. Acta Veterinaria Hungarica 2016, 64: 497-513. PMID: 27993100, DOI: 10.1556/004.2016.046.Peer-Reviewed Original Research
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
The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry
Hess ME, Hess S, Meyer KD, Verhagen LA, Koch L, Brönneke HS, Dietrich MO, Jordan SD, Saletore Y, Elemento O, Belgardt BF, Franz T, Horvath TL, Rüther U, Jaffrey SR, Kloppenburg P, Brüning JC. The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry. Nature Neuroscience 2013, 16: 1042-1048. PMID: 23817550, DOI: 10.1038/nn.3449.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAlpha-Ketoglutarate-Dependent Dioxygenase FTOAnimalsCocaineCorpus StriatumDopamineDopaminergic NeuronsExploratory BehaviorFemaleG Protein-Coupled Inwardly-Rectifying Potassium ChannelsLocomotionMaleMesencephalonMethylationMethyltransferasesMiceMice, Inbred C57BLMice, KnockoutMixed Function OxygenasesOxo-Acid-LyasesPhenotypeQuinpiroleReceptors, Dopamine D2Receptors, Dopamine D3RewardRNA Processing, Post-TranscriptionalRNA, MessengerSignal Transduction
2011
Obesity is associated with hypothalamic injury in rodents and humans
Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR, Nguyen HT, Fischer JD, Matsen ME, Wisse BE, Morton GJ, Horvath TL, Baskin DG, Tschöp MH, Schwartz MW. Obesity is associated with hypothalamic injury in rodents and humans. Journal Of Clinical Investigation 2011, 122: 153-162. PMID: 22201683, PMCID: PMC3248304, DOI: 10.1172/jci59660.Peer-Reviewed Original ResearchConceptsHigh-fat dietHFD feedingMediobasal hypothalamusPeripheral tissuesRodent modelsBody weight controlHypothalamic arcuate nucleusSubstantial weight gainConsequences of obesityNeuron injuryHypothalamic injuryNeuronal injuryNeuroprotective mechanismsReactive gliosisObese humansHypothalamic areaArcuate nucleusInflammatory signalingBrain areasWeight controlObesityGliosisEnergy homeostasisWeight gainInflammationHigh-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons
Klöckener T, Hess S, Belgardt BF, Paeger L, Verhagen LA, Husch A, Sohn JW, Hampel B, Dhillon H, Zigman JM, Lowell BB, Williams KW, Elmquist JK, Horvath TL, Kloppenburg P, Brüning JC. High-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons. Nature Neuroscience 2011, 14: 911-918. PMID: 21642975, PMCID: PMC3371271, DOI: 10.1038/nn.2847.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAge FactorsAnimalsAnimals, NewbornBlood GlucoseBody WeightCalorimetryDietary FatsDose-Response Relationship, DrugEatingEnzyme InhibitorsEnzyme-Linked Immunosorbent AssayFemaleGene Expression RegulationGlucose Tolerance TestGreen Fluorescent ProteinsHypoglycemic AgentsIn Vitro TechniquesInjections, IntraventricularInsulinLeptinMaleMiceMice, Inbred C57BLMice, TransgenicNeuronsObesityPatch-Clamp TechniquesPhosphatidylinositol 3-KinasesReceptor, InsulinRNA, MessengerSignal TransductionSteroidogenic Factor 1Time FactorsTolbutamideVentromedial Hypothalamic Nucleus
2010
Early-Life Experience Reduces Excitation to Stress-Responsive Hypothalamic Neurons and Reprograms the Expression of Corticotropin-Releasing Hormone
Korosi A, Shanabrough M, McClelland S, Liu ZW, Borok E, Gao XB, Horvath TL, Baram TZ. Early-Life Experience Reduces Excitation to Stress-Responsive Hypothalamic Neurons and Reprograms the Expression of Corticotropin-Releasing Hormone. Journal Of Neuroscience 2010, 30: 703-713. PMID: 20071535, PMCID: PMC2822406, DOI: 10.1523/jneurosci.4214-09.2010.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnalysis of VarianceAnimalsAnimals, NewbornChromatin ImmunoprecipitationCorticotropin-Releasing HormoneExcitatory Amino Acid AntagonistsFemaleGene Expression Regulation, DevelopmentalMaleMaternal DeprivationMicroscopy, Electron, TransmissionNeuronsParaventricular Hypothalamic NucleusPatch-Clamp TechniquesPhysical StimulationPregnancyRatsRats, Sprague-DawleyRepressor ProteinsRNA, MessengerSodium Channel BlockersStress, PsychologicalSynaptic PotentialsTetrodotoxinVesicular Glutamate Transport Protein 2ConceptsCorticotropin-releasing hormoneNeuron-restrictive silencer factorCRH neuronsHypothalamic neuronsCRH expressionEarly life experiencesMiniature excitatory synaptic currentsHypothalamic CRH neuronsExcitatory synaptic currentsCRH gene expressionGlutamate vesicular transporterCRH gene transcriptionTranscriptional repressor neuron-restrictive silencer factorExcitatory innervationExperience-induced neuroplasticityInhibitory synapsesRat pupsExcitatory synapsesSynaptic currentsPersistent suppressionVesicular transportersCognitive functionNeuronsSilencer factorMaternal care
2009
Ghrelin Promotes and Protects Nigrostriatal Dopamine Function via a UCP2-Dependent Mitochondrial Mechanism
Andrews ZB, Erion D, Beiler R, Liu ZW, Abizaid A, Zigman J, Elsworth JD, Savitt JM, DiMarchi R, Tschöp M, Roth RH, Gao XB, Horvath TL. Ghrelin Promotes and Protects Nigrostriatal Dopamine Function via a UCP2-Dependent Mitochondrial Mechanism. Journal Of Neuroscience 2009, 29: 14057-14065. PMID: 19906954, PMCID: PMC2845822, DOI: 10.1523/jneurosci.3890-09.2009.Peer-Reviewed Original ResearchConceptsDA cell lossNigrostriatal dopamine functionParkinson's diseaseDopamine functionCell lossSubstantia nigra pars compactaSNpc DA neuronsStriatal dopamine levelsStriatal dopamine lossExogenous ghrelin administrationLoss of appetiteDopamine cell degenerationNovel therapeutic strategiesMitochondrial mechanismsTyrosine hydroxylase mRNAReactive oxygen species productionMPTP treatmentPeripheral ghrelinSNpc cellsTetrahydropyridine (MPTP) treatmentDA neuronsDopamine lossGhrelin administrationPars compactaCatecholaminergic neuronsEstrogens 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
Bsx, a Novel Hypothalamic Factor Linking Feeding with Locomotor Activity, Is Regulated by Energy Availability
Nogueiras R, López M, Lage R, Perez-Tilve D, Pfluger P, Mendieta-Zerón H, Sakkou M, Wiedmer P, Benoit SC, Datta R, Dong JZ, Culler M, Sleeman M, Vidal-Puig A, Horvath T, Treier M, Diéguez C, Tschöp M. Bsx, a Novel Hypothalamic Factor Linking Feeding with Locomotor Activity, Is Regulated by Energy Availability. Endocrinology 2008, 149: 3009-3015. PMID: 18308842, PMCID: PMC2408820, DOI: 10.1210/en.2007-1684.Peer-Reviewed Original ResearchConceptsHigh-fat dietArcuate nucleusLeptin resistanceMelanocortin-4 receptor knockout miceObese leptin-deficient miceAgouti gene-related proteinCentral nervous system controlNovel hypothalamic factorPeripheral energy balanceOrexigenic neuropeptide YReceptor knockout miceSpontaneous physical activityGhrelin receptor antagonistLeptin-deficient miceNervous system controlEnergy balance signalsFasting-induced increaseGene-related proteinGhrelin administrationLeptin injectionPharmacological modificationNeuropeptide YGhrelin signalingHypothalamic factorsReceptor antagonist
2007
Simultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure
Pfluger PT, Kirchner H, Günnel S, Schrott B, Perez-Tilve D, Fu S, Benoit SC, Horvath T, Joost HG, Wortley KE, Sleeman MW, Tschöp M. Simultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure. AJP Gastrointestinal And Liver Physiology 2007, 294: g610-g618. PMID: 18048479, DOI: 10.1152/ajpgi.00321.2007.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsAnthropometryBlood GlucoseBody CompositionBody TemperatureBody WeightEatingEnergy MetabolismGene DeletionGenotypeGhrelinGlucose Tolerance TestInsulin ResistanceLigandsLipidsMiceMice, KnockoutMotor ActivityReceptors, GhrelinReverse Transcriptase Polymerase Chain ReactionRNA, MessengerConceptsFood intakeSimultaneous deletionStandard dietHigh-fat diet-induced obesityMotor activityWild-type control miceFirst mouse mutantsMetabolic phenotypeDiet-induced obesityEnergy metabolism phenotypesEnergy expenditureGene-deficient miceKnockout mice exhibitSingle gene-deficient miceSame genetic backgroundMost speciesWT miceControl miceStandard chowMolecular controlBody adiposityBiological roleLean massMouse mutantsMeal patterns
2003
Uncoupling Protein 2 Prevents Neuronal Death Including that Occurring during Seizures: A Mechanism for Preconditioning
Diano S, Matthews RT, Patrylo P, Yang L, Beal MF, Barnstable CJ, Horvath TL. Uncoupling Protein 2 Prevents Neuronal Death Including that Occurring during Seizures: A Mechanism for Preconditioning. Endocrinology 2003, 144: 5014-5021. PMID: 12960023, DOI: 10.1210/en.2003-0667.Peer-Reviewed Original ResearchConceptsFree radical-induced cell deathFree radical-induced damageCell deathSeizure inductionSeizure activityNeuronal deathRadical-induced damageTransgenic miceNeurodegenerative disordersCellular stressRobust reductionUCP2 levelsParallel decreaseDeathATP levelsPC12 cellsProtein 2Mitochondrial uncoupling proteinUCP2Mitochondrial numberCellular energy productionFree radicalsHarmful effectsUncoupling proteinEpilepsyCoenzyme Q Induces Nigral Mitochondrial Uncoupling and Prevents Dopamine Cell Loss in a Primate Model of Parkinson’s Disease
Horvath TL, Diano S, Leranth C, Garcia-Segura LM, Cowley MA, Shanabrough M, Elsworth JD, Sotonyi P, Roth RH, Dietrich EH, Matthews RT, Barnstable CJ, Redmond DE. Coenzyme Q Induces Nigral Mitochondrial Uncoupling and Prevents Dopamine Cell Loss in a Primate Model of Parkinson’s Disease. Endocrinology 2003, 144: 2757-2760. PMID: 12810526, DOI: 10.1210/en.2003-0163.Peer-Reviewed Original ResearchConceptsDopamine cell lossParkinson's diseaseCell lossShort-term oral administrationMitochondrial uncouplingSubstantia nigraDopamine neuronsTetrahydropyridine (MPTP) administrationCoenzyme QPrimate modelOral administrationDiseaseOxidative stressState 4 respirationMitochondrial uncoupling proteinAdministrationUncoupling proteinUncouplingNeuronsNigraTetrahydropyridine
2002
ER-X: A Novel, Plasma Membrane-Associated, Putative Estrogen Receptor That Is Regulated during Development and after Ischemic Brain Injury
Toran-Allerand CD, Guan X, MacLusky NJ, Horvath TL, Diano S, Singh M, Connolly ES, Nethrapalli S, Tinnikov AA. ER-X: A Novel, Plasma Membrane-Associated, Putative Estrogen Receptor That Is Regulated during Development and after Ischemic Brain Injury. Journal Of Neuroscience 2002, 22: 8391-8401. PMID: 12351713, PMCID: PMC6757764, DOI: 10.1523/jneurosci.22-19-08391.2002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding, CompetitiveBlotting, WesternBrain IschemiaCaveolaeCell MembraneCell-Free SystemCells, CulturedCholesterolEnzyme ActivationEstradiolGene Expression Regulation, DevelopmentalIonophoresMiceMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesNeocortexNeuronsReceptors, EstrogenRNA, MessengerSignal TransductionSubcellular FractionsSubstrate SpecificityConceptsMAPK cascadePlasma membraneExtracellular signal-regulated kinases ERK1Neuronal differentiationPlasma membrane-associatedPlasma membrane-associated ERsProtein kinase isoformsCell-free systemMembrane-associated ERER alphaPutative ERKinases ERK1Cell divisionER betaSustained phosphorylationKinase isoformsERK activationMembrane-associatedGene-disrupted miceNovel mechanismEstrogen receptorUterine plasma membranesInhibitory regulatorIschemic stroke injuryIschemic brain injuryUncoupling protein 2 (UCP2) lowers alcohol sensitivity and pain threshold
Horvath B, Spies C, Horvath G, Kox WJ, Miyamoto S, Barry S, Warden CH, Bechmann I, Diano S, Heemskerk J, Horvath TL. Uncoupling protein 2 (UCP2) lowers alcohol sensitivity and pain threshold. Biochemical Pharmacology 2002, 64: 369-374. PMID: 12147287, DOI: 10.1016/s0006-2952(02)01167-x.Peer-Reviewed Original ResearchConceptsCentral nervous systemTemperature sensationNervous systemBasal forebrain areasMajor risk factorAcute ethanol exposureAcute alcohol consumptionImpairment of painPeripheral energy expenditureAbuse of ethanolProtein 2Ethanol-induced toleranceWild-type animalsUCP2 knockoutPain thresholdTime of recoveryInduces toleranceRisk factorsEthanol exposureForebrain areasAxon terminalsNeuronal responsesAcute exposureAlcohol consumptionEnergy homeostasis
2000
Mitochondrial Uncoupling Protein 2 (UCP2) in the Nonhuman Primate Brain and Pituitary*This work was supported by NSF Grant IBN-9728581, NIH Grants NS-36111, MH-59847, RR-00163, HD-29186, and HD-37186.
Diano S, Urbanski H, Horvath B, Bechmann I, Kagiya A, Nemeth G, Naftolin F, Warden C, Horvath T. Mitochondrial Uncoupling Protein 2 (UCP2) in the Nonhuman Primate Brain and Pituitary*This work was supported by NSF Grant IBN-9728581, NIH Grants NS-36111, MH-59847, RR-00163, HD-29186, and HD-37186. Endocrinology 2000, 141: 4226-4238. PMID: 11089557, DOI: 10.1210/endo.141.11.7740.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain ChemistryChlorocebus aethiopsCorticotropin-Releasing HormoneGene ExpressionHypothalamusImmunohistochemistryIn Situ HybridizationIon ChannelsLimbic SystemMacaca fascicularisMacaca mulattaMembrane Transport ProteinsMicroscopy, FluorescenceMitochondrial ProteinsNeuropeptide YOxytocinPituitary GlandPituitary Gland, AnteriorPituitary Gland, PosteriorProteinsRNA, MessengerUncoupling Protein 2VasopressinsConceptsUncoupling protein 2Pituitary glandAnterior lobePrimate brainAxonal processesBrain stem regionsNonhuman primate brainSitu hybridization histochemistryMessenger RNACentral autonomicRR-00163Mitochondrial uncoupling protein 2Neuropeptide YPrimate hypothalamusAnterior pituitaryMetabolic disordersRodent brainPosterior lobeHybridization histochemistryPOMC cellsCell bodiesUCP2 expressionRodent dataNovel targetBrain
1999
Brain Uncoupling Protein 2: Uncoupled Neuronal Mitochondria Predict Thermal Synapses in Homeostatic Centers
Horvath T, Warden C, Hajos M, Lombardi A, Goglia F, Diano S. Brain Uncoupling Protein 2: Uncoupled Neuronal Mitochondria Predict Thermal Synapses in Homeostatic Centers. Journal Of Neuroscience 1999, 19: 10417-10427. PMID: 10575039, PMCID: PMC6782406, DOI: 10.1523/jneurosci.19-23-10417.1999.Peer-Reviewed Original ResearchConceptsC-Fos-expressing cellsPeripheral energy homeostasisHormone-releasing hormoneHypothalamic neuronal populationsCorticotropin-releasing factorMelanin-concentrating hormoneMitochondria of neuronsUCP2 proteinPeripheral hormonesProximal dendritesNeuropeptide YGonadal steroidsModulates neurotransmissionAxon terminalsBasal brainLocal brainNeuronal populationsAxonal processesNeuronal mitochondriaPeptidergic circuitsBrain circuitsEnergy homeostasisCold exposureNeuronsEndocrine processesEstrogen receptor β and progesterone receptor mRNA in the intergeniculate leaflet of the female rat
Horvath T, Diano S, Sakamoto H, Shughrue P, Merchenthaler I. Estrogen receptor β and progesterone receptor mRNA in the intergeniculate leaflet of the female rat. Brain Research 1999, 844: 196-200. PMID: 10536277, DOI: 10.1016/s0006-8993(99)01759-x.Peer-Reviewed Original ResearchConceptsLateral geniculate bodyEstrogen receptor betaLateral geniculate nucleusGeniculate bodyIntergeniculate leafletProgesterone receptorGeniculate nucleusReceptor mRNAReceptor betaDorsal lateral geniculate nucleusVentral lateral geniculate nucleusProgesterone receptor mRNAHypothalamic neuroendocrine cellsEstrogen receptor βHormone receptor mRNADifferent limbicHypothalamic sitesFemale ratsCentral regulationReceptor βLabeled cellsNeuroendocrine mechanismsNeuroendocrine cellsEndocrine mechanismsPopulation of cells
1998
Monosynaptic Pathway Between the Arcuate Nucleus Expressing Glial Type II Iodothyronine 5′‐Deiodinase mRNA and the Median Eminence‐Projective TRH Cells of the Rat Paraventricular Nucleus
Diano S, Naftolin F, Goglia F, Csernus V, Horvath T. Monosynaptic Pathway Between the Arcuate Nucleus Expressing Glial Type II Iodothyronine 5′‐Deiodinase mRNA and the Median Eminence‐Projective TRH Cells of the Rat Paraventricular Nucleus. Journal Of Neuroendocrinology 1998, 10: 731-742. PMID: 9792325, DOI: 10.1046/j.1365-2826.1998.00204.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArcuate Nucleus of HypothalamusFemaleFluorescent DyesImmunohistochemistryIn Situ HybridizationIodide PeroxidaseIsoenzymesMaleMedian EminenceNeural PathwaysNeurogliaParaventricular Hypothalamic NucleusPhytohemagglutininsRatsRats, Sprague-DawleyRNA, MessengerStilbamidinesThyrotropin-Releasing HormoneFasting-Induced Increase in Type II Iodothyronine Deiodinase Activity and Messenger Ribonucleic Acid Levels Is Not Reversed by Thyroxine in the Rat Hypothalamus
Diano S, Naftolin F, Goglia F, Horvath T. Fasting-Induced Increase in Type II Iodothyronine Deiodinase Activity and Messenger Ribonucleic Acid Levels Is Not Reversed by Thyroxine in the Rat Hypothalamus. Endocrinology 1998, 139: 2879-2884. PMID: 9607797, DOI: 10.1210/endo.139.6.6062.Peer-Reviewed Original Research