2016
Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes
Romanov RA, Zeisel A, Bakker J, Girach F, Hellysaz A, Tomer R, Alpár A, Mulder J, Clotman F, Keimpema E, Hsueh B, Crow AK, Martens H, Schwindling C, Calvigioni D, Bains JS, Máté Z, Szabó G, Yanagawa Y, Zhang MD, Rendeiro A, Farlik M, Uhlén M, Wulff P, Bock C, Broberger C, Deisseroth K, Hökfelt T, Linnarsson S, Horvath TL, Harkany T. Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes. Nature Neuroscience 2016, 20: 176-188. PMID: 27991900, PMCID: PMC7615022, DOI: 10.1038/nn.4462.Peer-Reviewed Original Research
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 neurons
2006
Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque
Downs JL, Dunn MR, Borok E, Shanabrough M, Horvath TL, Kohama SG, Urbanski HF. Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque. Neurobiology Of Aging 2006, 28: 1286-1295. PMID: 16870307, DOI: 10.1016/j.neurobiolaging.2006.05.025.Peer-Reviewed Original ResearchConceptsLateral hypothalamic areaPoor sleep qualityLocus coeruleusNoradrenergic locus coeruleusSleep qualityNeuron numberRhesus macaquesAge-related decreaseTyrosine hydroxylase mRNAAge-related lossMale rhesus macaquesOrexin innervationOrexin neuronsOrexin neuropeptidesAge-related declineB immunoreactivityHypothalamic areaNeuronal changesElderly humansAxon densityLC contributeHydroxylase mRNANonhuman primatesOld animalsAdult animalsUncoupling protein‐2 promotes nigrostriatal dopamine neuronal function
Andrews ZB, Rivera A, Elsworth JD, Roth RH, Agnati L, Gago B, Abizaid A, Schwartz M, Fuxe K, Horvath TL. Uncoupling protein‐2 promotes nigrostriatal dopamine neuronal function. European Journal Of Neuroscience 2006, 24: 32-36. PMID: 16882005, DOI: 10.1111/j.1460-9568.2006.04906.x.Peer-Reviewed Original ResearchMeSH Keywords3,4-Dihydroxyphenylacetic AcidAnimalsCorpus StriatumDopamineDopamine Plasma Membrane Transport ProteinsImmunohistochemistryIon ChannelsMaleMembrane Transport ProteinsMiceMice, KnockoutMitochondrial ProteinsMotor ActivityNeuronsSubstantia NigraTyrosine 3-MonooxygenaseUncoupling Protein 2ConceptsSubstantia nigra pars compactaDopamine neuronal functionUCP2-KO miceParkinson's diseaseNeuronal functionNigrostriatal dopamine functionTyrosine hydroxylase immunoreactivityUCP2 knockout miceDopamine transporter immunoreactivityProtein 2Wild-type controlsHydroxylase immunoreactivityPars compactaDopamine turnoverTransporter immunoreactivityDopamine ratioBehavioral deficitsLocomotor functionNucleus accumbensBiochemical deficitsDopamine functionBrain regionsNeurological pathologiesDiseaseMice
2005
Uncoupling protein 2 protects dopaminergic neurons from acute 1,2,3,6‐methyl‐phenyl‐tetrahydropyridine toxicity
Conti B, Sugama S, Lucero J, Winsky‐Sommerer R, Wirz SA, Maher P, Andrews Z, Barr AM, Morale MC, Paneda C, Pemberton J, Gaidarova S, Behrens MM, Beal F, Sanna PP, Horvath T, Bartfai T. Uncoupling protein 2 protects dopaminergic neurons from acute 1,2,3,6‐methyl‐phenyl‐tetrahydropyridine toxicity. Journal Of Neurochemistry 2005, 93: 493-501. PMID: 15816872, DOI: 10.1111/j.1471-4159.2005.03052.x.Peer-Reviewed Original ResearchConceptsDopaminergic neuronsParkinson's diseaseOxidative stressSpecific neuronal expressionTyrosine hydroxylase promoterTetrahydropyridine (MPTP) toxicityCatecholaminergic neuronsSubstantia nigraHydroxylase promoterLocomotor functionMouse modelNeuronal expressionAcute exposureTransgenic miceSporadic formsTwofold elevationUCP2 expressionDiseaseMarked reductionNeuronsMiceNeuroprotectionProtein 2UCP familyDrug targets
2004
Direct visual and circadian pathways target neuroendocrine cells in primates
Abizaid A, Horvath B, Keefe DL, Leranth C, Horvath TL. Direct visual and circadian pathways target neuroendocrine cells in primates. European Journal Of Neuroscience 2004, 20: 2767-2776. PMID: 15548220, DOI: 10.1111/j.1460-9568.2004.03737.x.Peer-Reviewed Original ResearchConceptsSuprachiasmatic nucleusRetinal inputNeuroendocrine cellsDirect retinal inputHormone-releasing hormoneNon-human primatesHypothalamic suprachiasmatic nucleusSCN efferentsHypothalamic areaHypothalamic neuronsHypothalamic sitesMonosynaptic pathwayVisual afferentsHypothalamic regulatorGonadal axisHormone releaseNeuroendocrine functionPituitary gonadotropsPhotic modulationNeuronsCircadian pacemakerVervet monkeysPresent studyTracing techniquesCircadian clock
2000
Estrogen Is Essential for Maintaining Nigrostriatal Dopamine Neurons in Primates: Implications for Parkinson's Disease and Memory
Leranth C, Roth R, Elsworth J, Naftolin F, Horvath T, Redmond D. Estrogen Is Essential for Maintaining Nigrostriatal Dopamine Neurons in Primates: Implications for Parkinson's Disease and Memory. Journal Of Neuroscience 2000, 20: 8604-8609. PMID: 11102464, PMCID: PMC6773080, DOI: 10.1523/jneurosci.20-23-08604.2000.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell CountCell SurvivalChlorocebus aethiopsDopamineDrug ImplantsEstrogensFemaleMaleMemoryNeuronsOvariectomyParkinson DiseaseSubstantia NigraTyrosine 3-MonooxygenaseConceptsNigrostriatal dopamine neuronsDopamine neuronsParkinson's diseaseSubstantia nigraDopamine cellsTyrosine hydroxylase-expressing neuronsTyrosine hydroxylase-immunoreactive cellsNigral dopamine systemsEstrogen replacement therapyNew treatment strategiesUnbiased stereological analysisTypes of neuronsProgression of diseaseEstrogen replacementPostmenopausal womenEstrogen deprivationReplacement therapyTreatment strategiesCompact zoneGonadal hormonesLong-term effectsDopamine systemEstrogenDiseaseNeuronsAMPA receptors colocalize with neuropeptide-Y- and galanin-containing, but not with dopamine, neurons of the female rat arcuate nucleus: a semiquantitative immunohistochemical colocalization study
Zsarnovszky A, Horvath T, Naftolin F, Leranth C. AMPA receptors colocalize with neuropeptide-Y- and galanin-containing, but not with dopamine, neurons of the female rat arcuate nucleus: a semiquantitative immunohistochemical colocalization study. Experimental Brain Research 2000, 133: 532-537. PMID: 10985687, DOI: 10.1007/s002210000425.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArcuate Nucleus of HypothalamusDopamineFemaleGalaninImmunohistochemistryNeuronsNeuropeptide YRatsRats, Sprague-DawleyReceptors, AMPATyrosine 3-MonooxygenaseConceptsArcuate nucleusAMPA receptorsFemale rat arcuate nucleusExcitatory amino acid neurotransmissionIsoxazole propionic acid (AMPA) receptorsAmino acid neurotransmissionTH-ir cellsMajor neuronal populationsRat arcuate nucleusPropionic acid receptorsHormone delivery systemsImmunohistochemical colocalization studiesGlutamatergic innervationGlutamatergic inputsFemale ratsNeuronal populationsGalaninAcid receptorsNeuronsReceptorsNPYNeuropeptidesColocalization studiesPresent studyDelivery systemEstrogen effects on tyrosine hydroxylase-immunoreactive cells in the ventral mesencephalon of the female rat: further evidence for the two cell hypothesis of dopamine function
Zsarnovszky A, Scalise T, Horvath T, Naftolin F. Estrogen effects on tyrosine hydroxylase-immunoreactive cells in the ventral mesencephalon of the female rat: further evidence for the two cell hypothesis of dopamine function. Brain Research 2000, 868: 363-366. PMID: 10854590, DOI: 10.1016/s0006-8993(00)02323-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell CountDopamineEstrogensFemaleNeural PathwaysNeuronsRatsRats, Sprague-DawleySexual Behavior, AnimalSubstantia NigraTyrosine 3-MonooxygenaseVentral Tegmental AreaConceptsSubstantia nigra compactaFemale ratsTyrosine hydroxylaseVentral mesencephalic dopaminergic neuronsTyrosine hydroxylase-immunoreactive cellsMesencephalic dopaminergic neuronsVentral tegmental areaTH-immunoreactive perikaryaDifferential effectsVentral mesencephalonTH immunoreactivityDopaminergic neuronsEstrogen effectsEstradiol benzoateTegmental areaMidbrain neuronsInterfascicular nucleusDopamine functionCell hypothesisRatsCell countingNeuronsPresent studyFurther evidenceOVX
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
Segregation 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 neuronsAn Alternate Pathway for Visual Signal Integration into the Hypothalamo-Pituitary Axis: Retinorecipient Intergeniculate Neurons Project to Various Regions of the Hypothalamus and Innervate Neuroendocrine Cells Including Those Producing Dopamine
Horvath TL. An Alternate Pathway for Visual Signal Integration into the Hypothalamo-Pituitary Axis: Retinorecipient Intergeniculate Neurons Project to Various Regions of the Hypothalamus and Innervate Neuroendocrine Cells Including Those Producing Dopamine. Journal Of Neuroscience 1998, 18: 1546-1558. PMID: 9454860, PMCID: PMC6792709, DOI: 10.1523/jneurosci.18-04-01546.1998.Peer-Reviewed Original ResearchConceptsHypothalamo-pituitary axisIntergeniculate leafletNeuroendocrine cellsSuprachiasmatic nucleusHypothalamic dopamine neuronsMedial preoptic areaFenestrated capillariesPopulations of neuronsNeurons projectBilateral enucleationHypothalamic projectionsDistal dendritesRetrograde tracerVentromedial nucleusDopamine neuronsIntraperitoneal injectionProjection sitesPeriventricular nucleusPreoptic areaRetinal fibersTract tracingHypothalamic cellsRetinal axonsSynaptic targetsEfferents
1997
Suprachiasmatic 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 hydroxylase
1995
Distribution of Estrogen Receptor-Immunoreactive Cells in Monkey Hypothalamus: Relationship to Neurones Containing Luteinizing Hormone-Releasing Hormone and Tyrosine Hydroxylase
Herbison A, Horvath T, Naftolin F, Leranth C. Distribution of Estrogen Receptor-Immunoreactive Cells in Monkey Hypothalamus: Relationship to Neurones Containing Luteinizing Hormone-Releasing Hormone and Tyrosine Hydroxylase. Neuroendocrinology 1995, 61: 1-10. PMID: 7731492, DOI: 10.1159/000126810.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChlorocebus aethiopsFemaleGonadotropin-Releasing HormoneHypothalamusImmunohistochemistryMacaca fascicularisNeuronsReceptors, EstrogenTyrosine 3-MonooxygenaseConceptsER-immunoreactive cellsHormone-releasing hormoneER immunoreactivityMonkey hypothalamusTyrosine hydroxylaseDouble-labeling experimentsProgesterone receptorDopaminergic neuronesLHRH neuronesEstrogen receptor-immunoreactive cellsReceptor-immunoreactive cellsPituitary hormone secretionSpecific hypothalamic nucleiTH-immunoreactive cellsPR-containing cellsDopamine-containing neuronesHypothalamic dopaminergic neuronesAfrican green monkeysLHRH neuronsPeriventricular areaSteroid statusArcuate nucleusHormone secretionHypothalamic nucleiPrimate hypothalamus
1993
Neuropeptide-Y innervation of estrogen-induced progesterone receptor-containing dopamine cells in the monkey hypothalamus: a triple labeling light and electron microscopic study
Horvath TL, Shanabrough M, Naftolin F, Leranth C. Neuropeptide-Y innervation of estrogen-induced progesterone receptor-containing dopamine cells in the monkey hypothalamus: a triple labeling light and electron microscopic study. Endocrinology 1993, 133: 405-414. PMID: 8100520, DOI: 10.1210/endo.133.1.8100520.Peer-Reviewed Original ResearchConceptsTyrosine hydroxylase-immunoreactive neuronsHydroxylase-immunoreactive neuronsProgesterone receptorSynaptic contactsAxon terminalsDopamine cellsTyrosine hydroxylase-immunopositive cellsHypophyseal hormone secretionEffects of NPYDorsomedial hypothalamic nucleusCoronal vibratome sectionsNuclear progesterone receptorPR-containing cellsAfrican green monkeysDiaminobenzidine reactionNPY axonsPeriventricular areaOVX animalsHormone secretionMonkey hypothalamusAnterior hypothalamusHypothalamic nucleiDopamine neuronsPRL releaseEstrogenLuteinizing Hormone‐Releasing Hormone and Gamma‐Aminobutyric Acid Neurons in the Medial Preoptic Area are Synaptic Targets of Dopamine Axons Originating in Anterior Periventricular Areas
Horvath T, Naftolin F, Leranth C. Luteinizing Hormone‐Releasing Hormone and Gamma‐Aminobutyric Acid Neurons in the Medial Preoptic Area are Synaptic Targets of Dopamine Axons Originating in Anterior Periventricular Areas. Journal Of Neuroendocrinology 1993, 5: 71-79. PMID: 8097941, DOI: 10.1111/j.1365-2826.1993.tb00365.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsCerebral VentriclesColchicineDopamineFemaleGamma-Aminobutyric AcidGlutamate DecarboxylaseGonadotropin-Releasing HormoneImmunohistochemistryMicroscopy, ElectronNeuronsOxidopaminePhytohemagglutininsPreoptic AreaRatsRats, Sprague-DawleySynapsesTissue FixationTyrosine 3-MonooxygenaseConceptsHormone-releasing hormoneMedial preoptic areaGlutamic acid decarboxylasePhaseolus vulgaris leucoagglutininZona incertaPreoptic areaTyrosine hydroxylaseGlutamic acid decarboxylase-immunoreactive neuronsDopamine axonsTyrosine hydroxylase-immunoreactive boutonsAcid decarboxylaseGamma-aminobutyric acid (GABA) neuronsRat medial preoptic areaAnterior periventricular areaDesipramine-pretreated ratsDopamine axon terminalsAnteroventral periventricular nucleusCell of originEarly morphological signsDopaminergic connectionsGABA neuronsGABA cellsPeriventricular areaAcute degenerationSynaptic contacts
1992
GABAergic and catecholaminergic innervation of mediobasal hypothalamic β-endorphin cells projecting to the medial preoptic area
Horvath TL, Naftolin F, Leranth C. GABAergic and catecholaminergic innervation of mediobasal hypothalamic β-endorphin cells projecting to the medial preoptic area. Neuroscience 1992, 51: 391-399. PMID: 1281529, DOI: 10.1016/0306-4522(92)90323-t.Peer-Reviewed Original ResearchConceptsMedial preoptic areaPreoptic areaHormone-producing cellsArcuate nucleusHypothalamic beta-endorphin neuronsHormone-releasing hormone (LHRH) neuronsBeta-endorphin neuronsDirect estrogen actionHormone-containing neuronsVentromedial arcuate nucleusRetrograde tracer horseradish peroxidasePro-opiomelanocortin (POMC) neuronsCellular estrogen receptorsPro-opiomelanocortin cellsTracer horseradish peroxidaseΒ-endorphin cellsHormone neuronsImmunoreactive neuronsCatecholaminergic innervationCatecholaminergic neuronsRetrograde tracingSynaptic contactsEstrogen actionCatecholamine fibersAxon terminalsBeta-endorphin innervation of dopamine neurons in the rat hypothalamus: a light and electron microscopic double immunostaining study
Horvath TL, Naftolin F, Leranth C. Beta-endorphin innervation of dopamine neurons in the rat hypothalamus: a light and electron microscopic double immunostaining study. Endocrinology 1992, 131: 1547-1555. PMID: 1354605, DOI: 10.1210/endo.131.3.1354605.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta-EndorphinDopamineFemaleHypothalamusImmunohistochemistryMicroscopy, ImmunoelectronNerve FibersNeuronsRatsRats, Inbred StrainsSynapsesTyrosine 3-MonooxygenaseConceptsDopamine neuronsZona incertaDopamine cellsSynaptic connectionsCell bodiesDouble immunostaining experimentsHypophyseal hormone secretionHypothalamic dopaminergic systemFemale rat brainHypothalamic dopaminergic neuronsDorsomedial hypothalamic nucleusDopamine cell bodiesReceptor-containing cellsDouble immunostaining studiesLight microscopic examinationPutative synaptic connectionsLH releaseDopamine innervationImmunoreactive boutonsPeriventricular areaDopaminergic neuronsPRL secretionSynaptic contactsArcuate nucleusHormone secretion