2017
Endothelial HIF-1α Enables Hypothalamic Glucose Uptake to Drive POMC Neurons
Varela L, Suyama S, Huang Y, Shanabrough M, Tschöp M, Gao XB, Giordano FJ, Horvath TL. Endothelial HIF-1α Enables Hypothalamic Glucose Uptake to Drive POMC Neurons. Diabetes 2017, 66: db161106. PMID: 28292966, PMCID: PMC5440016, DOI: 10.2337/db16-1106.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalBlotting, WesternEndotheliumEnergy MetabolismFood DeprivationGene Knockdown TechniquesGlucoseHyperphagiaHypothalamusHypoxia-Inducible Factor 1, alpha SubunitImmunohistochemistryMiceMicroscopy, ElectronMitochondriaNeuronsPatch-Clamp TechniquesPro-OpiomelanocortinReal-Time Polymerase Chain ReactionConceptsPOMC neuronsGlucose uptakePOMC neuronal activityHypothalamic proopiomelanocortin (POMC) neuronsHypoxia-inducible factor-1αProopiomelanocortin neuronsVascular impairmentGlucose administrationMetabolic disordersNeuronal activityMetabolic environmentFactor-1αImpaired functioningEndothelial cellsNeuronsFood deprivationVivoCentral controlHypothalamusMiceAdministrationUptakeImpairment
2016
Mitochondria controlled by UCP2 determine hypoxia-induced synaptic remodeling in the cortex and hippocampus
Varela L, Schwartz ML, Horvath TL. Mitochondria controlled by UCP2 determine hypoxia-induced synaptic remodeling in the cortex and hippocampus. Neurobiology Of Disease 2016, 90: 68-74. PMID: 26777666, DOI: 10.1016/j.nbd.2016.01.004.Peer-Reviewed Original ResearchConceptsHippocampal neuronsMitochondria-endoplasmic reticulum interactionUCP2-KO miceEarly postnatal exposureLoss of synapsesOxygen tensionHigher brain regionsAdaptive mitochondrial responsesProtein 2 expressionHypothalamic circuitsPostnatal exposureKO miceSynaptic remodelingSystemic metabolismSynaptic inputsBrain cellsMetabolic controlNeuronal mitochondriaBrain regionsAdaptive responseNeuronsHippocampusMitochondrial dynamicsMetabolic challengesCortex
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
2012
Loss of Autophagy in Pro-opiomelanocortin Neurons Perturbs Axon Growth and Causes Metabolic Dysregulation
Coupé B, Ishii Y, Dietrich MO, Komatsu M, Horvath TL, Bouret SG. Loss of Autophagy in Pro-opiomelanocortin Neurons Perturbs Axon Growth and Causes Metabolic Dysregulation. Cell Metabolism 2012, 15: 247-255. PMID: 22285542, PMCID: PMC3278575, DOI: 10.1016/j.cmet.2011.12.016.Peer-Reviewed Original ResearchMeSH KeywordsAdiposityAnimalsArcuate Nucleus of HypothalamusAutophagyAutophagy-Related Protein 7AxonsBody WeightGlucose IntoleranceImmunoblottingMetabolic Networks and PathwaysMiceMicroscopy, ElectronMicrotubule-Associated ProteinsNeuronsPro-OpiomelanocortinTranscription Factor TFIIHTranscription FactorsUbiquitinConceptsPOMC neuronsHypothalamic melanocortin systemPathogenesis of obesityImportant intracellular mechanismNormal metabolic regulationP62-positive aggregatesFunctional neural systemsGlucose intoleranceAge-dependent accumulationNeonatal lifeAxonal projectionsMetabolic dysregulationMetabolic impairmentMelanocortin systemEssential autophagy geneBody weightLoss of autophagyMajor negative regulatorAxon growthIntracellular mechanismsNeuronsAutophagy deficiencyNeural developmentDirect genetic evidenceAtg7
2010
Direct inhibition of hypocretin/orexin neurons in the lateral hypothalamus by nociceptin/orphanin FQ blocks stress-induced analgesia in rats
Gerashchenko D, Horvath TL, Xie X. Direct inhibition of hypocretin/orexin neurons in the lateral hypothalamus by nociceptin/orphanin FQ blocks stress-induced analgesia in rats. Neuropharmacology 2010, 60: 543-549. PMID: 21195099, PMCID: PMC3031765, DOI: 10.1016/j.neuropharm.2010.12.026.Peer-Reviewed Original ResearchMeSH KeywordsAnalgesiaAnalysis of VarianceAnimalsCell CountHypothalamic Area, LateralImmunohistochemistryIntracellular Signaling Peptides and ProteinsMaleMicroinjectionsMicroscopy, ElectronNeuronsNeuropeptidesOpioid PeptidesOrexinsPain MeasurementPain PerceptionProto-Oncogene Proteins c-fosRatsRats, Sprague-DawleyReceptors, OpioidRestraint, PhysicalStatistics, NonparametricStress, PhysiologicalConceptsStress-induced analgesiaHcrt neuronsLateral hypothalamusPerifornical areaNociceptin/orphanin FQ systemHypocretin/orexin neuronsNociceptin/orphanin FQHcrt neuronal activityDirect inhibitionThermal pain thresholdThermal nociceptive testsHypocretin/orexinFos immunohistochemistryOrexin neuronsBilateral microinjectionIntracerebroventricular injectionPain thresholdNociceptive testsOrphanin FQOFQ receptorMouse modelNeuronal activityBrain areasHypothalamusNeuronsSynaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity
Horvath TL, Sarman B, García-Cáceres C, Enriori PJ, Sotonyi P, Shanabrough M, Borok E, Argente J, Chowen JA, Perez-Tilve D, Pfluger PT, Brönneke HS, Levin BE, Diano S, Cowley MA, Tschöp MH. Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 14875-14880. PMID: 20679202, PMCID: PMC2930476, DOI: 10.1073/pnas.1004282107.Peer-Reviewed Original ResearchConceptsHigh-fat dietSynaptic input organizationReactive gliosisPOMC neuronsDIO ratsDR ratsArcuate nucleusMelanocortin systemPOMC cellsNeuropeptide Y cellsInput organizationLoss of synapsesDiet-induced obesityBlood-brain barrierHFD-fed animalsDIO animalsAnorexigenic proopiomelanocortinGlial ensheathmentSynaptic organizationInhibitory inputsLean ratsDR animalsNeuronal circuitsCell bodiesGliosis
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 expenditureAdiposity
2004
CPG2 A brain- and synapse-specific protein that regulates the endocytosis of glutamate receptors
Cottrell JR, Borok E, Horvath TL, Nedivi E. CPG2 A brain- and synapse-specific protein that regulates the endocytosis of glutamate receptors. Neuron 2004, 44: 677-690. PMID: 15541315, PMCID: PMC3065105, DOI: 10.1016/j.neuron.2004.10.025.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBlotting, NorthernBlotting, WesternBrainCells, CulturedClathrin-Coated VesiclesEndocytosisHumansIn Situ HybridizationMicroscopy, ElectronMolecular Sequence DataNerve Tissue ProteinsNeuronal PlasticityNeuronsReceptors, AMPAReceptors, GlutamateReceptors, N-Methyl-D-AspartateReverse Transcriptase Polymerase Chain ReactionSynapsesConceptsGlutamate receptorsClathrin-coated vesiclesBrain-specific splice variantSynapse-specific proteinsExcitatory synapsesReceptor endocytosisSYNE-1 geneConstitutive internalizationEndocytic mechanismsSynaptic AMPA receptorsDendritic spine sizeMembrane transportSplice variantsSynaptic proteinsNMDA receptorsAMPA receptorsProteinPostsynaptic plasticityNeurotransmitter receptorsEndocytosisSynaptic strengthLong-term maintenanceReceptorsSpine sizeInternalizationPresynaptic N‐methyl‐D‐aspartate receptor expression is increased by estrogen in an aromatase‐rich area of the songbird hippocampus
Saldanha CJ, Schlinger BA, Micevych PE, Horvath TL. Presynaptic N‐methyl‐D‐aspartate receptor expression is increased by estrogen in an aromatase‐rich area of the songbird hippocampus. The Journal Of Comparative Neurology 2004, 469: 522-534. PMID: 14755533, DOI: 10.1002/cne.11035.Peer-Reviewed Original ResearchConceptsHP neuronsVertebrate hippocampusSongbird hippocampusN-methyl-d-aspartate receptor expressionSubcellular characteristicsInfluence of estrogenFunctional plasticityType glutamate receptorsZebra finch brainPrecise mechanismSomal sizeExcitatory pathwaysReceptor expressionExcitatory neurotransmissionExcitatory synapsesGlutamate receptorsPostsynaptic locusPresynaptic boutonsHippocampusEstrogenKey interfacePlasticityNeuronsAromataseAutoreception
2003
Estradiol affects axo-somatic contacts of neuroendocrine cells in the arcuate nucleus of adult rats
Parducz A, Zsarnovszky A, Naftolin F, Horvath TL. Estradiol affects axo-somatic contacts of neuroendocrine cells in the arcuate nucleus of adult rats. Neuroscience 2003, 117: 791-794. PMID: 12654332, DOI: 10.1016/s0306-4522(02)00967-3.Peer-Reviewed Original ResearchConceptsAxo-somatic contactsArcuate nucleusSynaptic plasticityGABAergic axo-somatic synapsesMorphological synaptic plasticityAxo-somatic synapsesEffects of estradiolSynapse quantificationArcuate neuronsTracer FluorogoldGonadal steroidsAnterior pituitaryAdult ratsHypophysiotropic neuronsMedian eminenceNervous systemTransient decreaseSystemic applicationNeuroendocrine cellsDisector methodNeuronsNumerical densityEstradiolFluorogoldCells
2001
A GABA-neuropeptide Y (NPY) interplay in LH release
Horvath T, Pu S, Dube M, Diano S, Kalra S. A GABA-neuropeptide Y (NPY) interplay in LH release. Peptides 2001, 22: 473-481. PMID: 11287104, DOI: 10.1016/s0196-9781(01)00343-6.Peer-Reviewed Original ResearchConceptsGamma-amino butyric acidLH releaseNeurotransmitter/neuromodulatorExcitatory effectsArcuate nucleusReceptor agonistInhibitory gamma-amino butyric acidY4 receptor agonistRelease of LHImmunoreactive axon terminalsRat brain sectionsDose-dependent mannerOvarian steroidsOvariectomized ratsAxon terminalsBrain sectionsPrimary siteNPYMorphological findingsCyclic releaseAgonistsLHNeuromodulatorsRatsAdministration
1999
Hypocretin (orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system
Horvath T, Peyron C, Diano S, Ivanov A, Aston‐Jones G, Kilduff T, van den Pol A. Hypocretin (orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system. The Journal Of Comparative Neurology 1999, 415: 145-159. PMID: 10545156, DOI: 10.1002/(sici)1096-9861(19991213)415:2<145::aid-cne1>3.0.co;2-2.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsChlorocebus aethiopsFemaleHypothalamusImmunohistochemistryIntracellular Signaling Peptides and ProteinsLocus CoeruleusMacaca fascicularisMaleMicroscopy, ElectronMSH Release-Inhibiting HormoneNeuropeptidesNeurotransmitter AgentsNorepinephrineOrexinsPresynaptic TerminalsRatsRats, Sprague-DawleyTetrodotoxinTyrosine 3-MonooxygenaseConceptsLocus coeruleusSynaptic innervationNoradrenergic systemAxon terminalsTyrosine hydroxylase-immunopositive cellsAsymmetrical synaptic contactsLC-noradrenergic systemParallel electrophysiological studiesLocus coeruleus noradrenergic systemPresence of tetrodotoxinMelanin-concentrating hormoneLC neuronsAutonomic centersNoradrenergic innervationDense arborizationsExcitatory responsesHypocretin cellsSubstantia nigraSynaptic contactsHypocretin-2Lateral hypothalamusZona incertaModest depolarizationCatecholamine systemsCentral regulation
1998
Tracing of the entorhinal‐hippocampal pathway in vitro
Kluge A, Hailer N, Horvath T, Bechmann I, Nitsch R. Tracing of the entorhinal‐hippocampal pathway in vitro. Hippocampus 1998, 8: 57-68. PMID: 9519887, DOI: 10.1002/(sici)1098-1063(1998)8:1<57::aid-hipo6>3.0.co;2-4.Peer-Reviewed Original ResearchConceptsOuter molecular layerPerforant pathDentate gyrusEntorhinal cortexEntorhinal-hippocampal interactionPerforant path axonsOrganotypic slice culturesMini-RubyPerforant fibersVitro tracingAnterograde degenerationDendritic shaftsLesion paradigmMicroglial cellsNeuronal degenerationEntorhinal neuronsNeurotoxin treatmentMolecular layerSlice culturesAxonal materialGrowth factorSubsequent phagocytosisGyrusEntorhinal-hippocampal regionFurther studiesLeptin Receptor Immunoreactivity is Associated with the Golgi Apparatus of Hypothalamic Neurones and Glial Cells
Diano S, Kalra S, Horvath T. Leptin Receptor Immunoreactivity is Associated with the Golgi Apparatus of Hypothalamic Neurones and Glial Cells. Journal Of Neuroendocrinology 1998, 10: 647-650. PMID: 9744481, DOI: 10.1046/j.1365-2826.1998.00261.x.Peer-Reviewed Original ResearchConceptsLeptin receptor immunoreactivityReceptor immunoreactivityPerikaryal membraneGlial cellsGolgi apparatusHypothalamic neuronesCentral nervous systemDifferent second messenger systemsHypothalamic neuronalPeripheral hormonesDentate gyrusSecond messenger systemsEndocrine functionLeptin receptorHypothalamic cellsNervous systemThyroid axisImmunoreactivityCentral mechanismsLeptinIntracellular mechanismsTrans cisternaeNeuronesMessenger systemsPredominant localizationSegregation of the intra- and extrahypothalamic neuropeptide Y and catecholaminergic inputs on paraventricular neurons, including those producing thyrotropin-releasing hormone
Diano S, Naftolin F, Goglia F, Horvath T. Segregation of the intra- and extrahypothalamic neuropeptide Y and catecholaminergic inputs on paraventricular neurons, including those producing thyrotropin-releasing hormone. Peptides 1998, 75: 117-126. PMID: 9802401, DOI: 10.1016/s0167-0115(98)00060-3.Peer-Reviewed Original ResearchConceptsParvicellular paraventricular nucleusMedian forebrain bundleProximal dendritesTRH neuronsDistal dendritesCell bodiesTRH cellsNPY inputAsymmetric synapsesCatecholaminergic inputsTyrosine hydroxylaseDendritic spinesInvolvement of NPYNumber of NPYThyrotropin-releasing hormone (TRH) mRNATH-immunoreactive fibersThyroid feedbackThyrotropin-releasing hormoneFood deprivationLight microscopic examinationTRH immunoreactive cellsNPY fibersNPY releaseHypothalamic NPYCatecholaminergic neuronsKainate 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
1997
Evidence for a direct neuronal pathway from the suprachiasmatic nucleus to the gonadotropin‐releasing hormone system: Combined tracing and light and electron microscopic immunocytochemical studies
Van Der Beek E, Horvath T, Wiegant V, Van Den Hurk R, Buijs R. Evidence for a direct neuronal pathway from the suprachiasmatic nucleus to the gonadotropin‐releasing hormone system: Combined tracing and light and electron microscopic immunocytochemical studies. The Journal Of Comparative Neurology 1997, 384: 569-579. PMID: 9259490, DOI: 10.1002/(sici)1096-9861(19970811)384:4<569::aid-cne6>3.0.co;2-0.Peer-Reviewed Original ResearchConceptsSuprachiasmatic nucleusFemale ratsGnRH systemGnRH-immunoreactive cell bodiesGonadotropin-releasing hormone (GnRH) neuronsDaily LH surgesImplantation of estrogenOvariectomized rats resultsRostral ventrolateral portionGonadotropin-releasing hormone (GnRH) systemVasoactive intestinal polypeptideElectron microscopic immunocytochemical studyHormone neuronsGnRH neuronsIntestinal polypeptideLH surgeMonosynaptic pathwayPutative transmittersAnterograde tracerPreoptic areaNeuronal pathwaysRats resultsVentrolateral portionBilateral projectionsFemale rodentsEvidence Showing That β-Endorphin Regulates Cyclic Guanosine 3′,5′-Monophosphate (cGMP) Efflux: Anatomical and Functional Support for an Interaction between Opiates and Nitric Oxide
Pu S, Horvath TL, Diano S, Naftolin F, Kalra PS, Kalra SP. Evidence Showing That β-Endorphin Regulates Cyclic Guanosine 3′,5′-Monophosphate (cGMP) Efflux: Anatomical and Functional Support for an Interaction between Opiates and Nitric Oxide. Endocrinology 1997, 138: 1537-1543. PMID: 9075713, DOI: 10.1210/endo.138.4.5086.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta-EndorphinCyclic GMPMicroscopy, ElectronMorphineNaloxoneNitric OxideNitric Oxide SynthasePreoptic AreaRatsConceptsExcitatory amino acidsMedial preoptic areaCGMP/Opioid influenceGnRH secretionNitric oxidePreoptic areaN-methyl-D-aspartate receptorsMu-opiate receptor agonistNOS-immunopositive cellsNOS-immunoreactive neuronsPituitary LH secretionOpiate receptor agonistsOpiate receptor antagonistRelease of GnRHCentral nervous systemDirect inhibitory controlExcitatory NMDATonic restraintLH secretionEndogenous opioidsNOS pathwayReceptor antagonistBeta-endorphinGonadal steroidsSuprachiasmatic efferents avoid phenestrated capillaries but innervate neuroendocrine cells, including those producing dopamine.
Horvath T. Suprachiasmatic efferents avoid phenestrated capillaries but innervate neuroendocrine cells, including those producing dopamine. Endocrinology 1997, 138: 1312-20. PMID: 9048641, DOI: 10.1210/endo.138.3.4976.Peer-Reviewed Original ResearchConceptsPituitary hormone secretionVasculosum laminae terminalisSuprachiasmatic nucleusHormone secretionNeuroendocrine cellsPreoptic areaLamina terminalisDopamine cellsMedian eminenceAnterior pituitary hormone secretionMedial preoptic areaDiffuse cytoplasmic labelingPhaseolus vulgaris leukoagglutininFluorogold labelingPeriventricular areaArcuate nucleusHypothalamic sitesIP administrationVentromedial nucleusAnterior hypothalamusAnterograde tracerAxon terminalsPeriventricular regionElectron microscopic examinationTyrosine hydroxylaseGonadal steroids target AMPA glutamate receptor-containing neurons in the rat hypothalamus, septum and amygdala: a morphological and biochemical study.
Diano S, Naftolin F, Horvath T. Gonadal steroids target AMPA glutamate receptor-containing neurons in the rat hypothalamus, septum and amygdala: a morphological and biochemical study. Endocrinology 1997, 138: 778-89. PMID: 9003015, DOI: 10.1210/endo.138.2.4937.Peer-Reviewed Original ResearchConceptsGonadal steroidsHypothalamic regionsExcitatory neurotransmissionAMPA receptorsReceptor-containing neuronsAMPA receptor expressionLevels of GluR1GluR2/3 expressionHormonal milieuHypothalamic areaFemale ratsAndrogen receptorDouble immunocytochemistryEstradiol treatmentHypothalamic functionReceptor expressionGlutamate receptorsEstrogen receptorBed nucleusHormonal treatmentRat hypothalamusHigh incidenceStimulatory influenceWestern blotHypothalamus