2021
Age‐related calcium dysregulation linked with tau pathology and impaired cognition in non‐human primates
Datta D, Leslie SN, Wang M, Morozov YM, Yang S, Mentone S, Zeiss C, Duque A, Rakic P, Horvath TL, van Dyck C, Nairn AC, Arnsten AFT. Age‐related calcium dysregulation linked with tau pathology and impaired cognition in non‐human primates. Alzheimer's & Dementia 2021, 17: 920-932. PMID: 33829643, PMCID: PMC8195842, DOI: 10.1002/alz.12325.Peer-Reviewed Original ResearchConceptsTau pathologyCalcium leakTau phosphorylationNeuronal firingAlzheimer's diseaseEarly tau phosphorylationPyramidal cell dendritesSporadic Alzheimer's diseasePrimary cortical neuronsPotential therapeutic targetCognitive performanceAge-related reductionMacaque dorsolateral prefrontal cortexDorsolateral prefrontal cortexNon-human primatesCalcium dysregulationCell dendritesCortical neuronsCalcium-binding proteinsAD biomarkersPathology markersTherapeutic targetAnimal modelsAged monkeysPrefrontal cortex
2020
Metabolic Lateralization in the Hypothalamus of Male Rats Related to Reproductive and Satiety States
Kiss DS, Toth I, Jocsak G, Bartha T, Frenyo LV, Barany Z, Horvath TL, Zsarnovszky A. Metabolic Lateralization in the Hypothalamus of Male Rats Related to Reproductive and Satiety States. Reproductive Sciences 2020, 27: 1197-1205. PMID: 32046448, PMCID: PMC7181557, DOI: 10.1007/s43032-019-00131-3.Peer-Reviewed Original ResearchConceptsSatiety stateMale ratsFood intakeImpact of gonadectomyRight hemisphereSleep-wake behaviorHypothalamic functionMale rodentsMetabolic asymmetryScheduled feedingFunctional lateralizationHypothalamusEx vivoRegulatory centersRatsMetabolic differencesHomeostatic processesFunctional asymmetryIntakeLateralizationRecent findingsPresent studyReproductive controlGonadectomySatiety
2019
Mediation of the Acute Stress Response by the Skeleton
Berger JM, Singh P, Khrimian L, Morgan DA, Chowdhury S, Arteaga-Solis E, Horvath TL, Domingos AI, Marsland AL, Yadav V, Rahmouni K, Gao XB, Karsenty G. Mediation of the Acute Stress Response by the Skeleton. Cell Metabolism 2019, 30: 890-902.e8. PMID: 31523009, PMCID: PMC6834912, DOI: 10.1016/j.cmet.2019.08.012.Peer-Reviewed Original ResearchConceptsStress responseBony vertebratesAcute stress responseBone-derived signalsWild-type animalsGenetic studiesEndocrine mediationAdrenal insufficient patientsVertebratesOsteocalcinSympathetic toneParasympathetic neuronsWildOsteocalcin levelsStressorsTypes of stressorsSelective surgeOsteoblastsInactivationRodentsResponseGlutamateUptake
2018
Hypothalamic CNTF volume transmission shapes cortical noradrenergic excitability upon acute stress
Alpár A, Zahola P, Hanics J, Hevesi Z, Korchynska S, Benevento M, Pifl C, Zachar G, Perugini J, Severi I, Leitgeb P, Bakker J, Miklosi AG, Tretiakov E, Keimpema E, Arque G, Tasan RO, Sperk G, Malenczyk K, Máté Z, Erdélyi F, Szabó G, Lubec G, Palkovits M, Giordano A, Hökfelt TG, Romanov RA, Horvath TL, Harkany T. Hypothalamic CNTF volume transmission shapes cortical noradrenergic excitability upon acute stress. The EMBO Journal 2018, 37: embj2018100087. PMID: 30209240, PMCID: PMC6213283, DOI: 10.15252/embj.2018100087.Peer-Reviewed Original ResearchConceptsHypothalamic activationVolume transmissionAcute stressNeurotrophic factor releaseNorepinephrinergic neuronsNoradrenergic neuronsCortical excitabilityMultimodal pathwaysNoradrenaline synthesisLocus coeruleusNeuronal excitationExtracellular signal-regulated kinases 1Norepinephrine synthesisTyrosine hydroxylaseEpendymal cellsSignal-regulated kinases 1ExcitabilityPrefrontal cortexFactor releaseCognate receptorsNeuronsHuman brainKinase 1CNTFActivationAltered Cortical and Hippocampal Excitability in TgF344-AD Rats Modeling Alzheimer’s Disease Pathology
Stoiljkovic M, Kelley C, Stutz B, Horvath TL, Hajós M. Altered Cortical and Hippocampal Excitability in TgF344-AD Rats Modeling Alzheimer’s Disease Pathology. Cerebral Cortex 2018, 29: 2716-2727. PMID: 29920597, PMCID: PMC7302691, DOI: 10.1093/cercor/bhy140.Peer-Reviewed Original ResearchConceptsTgF344-AD ratsHippocampal theta oscillationsAlzheimer's diseaseDisease pathologyTheta-phase gamma-amplitude couplingAge-matched wild-type counterpartsAD pathological featuresDisease-modifying therapiesAccumulation of amyloidPredictive animal modelsAlzheimer's disease pathologyHigh-voltage spindlesTheta oscillationsSignificant age-dependent declineAge-dependent declineHippocampal excitabilitySharp-wave ripplesAβ accumulationNeuronal lossAD ratsPathological featuresUrethane anesthesiaAD patientsAuditory gatingAD drugsComparative Analysis of Zearalenone Effects on Thyroid Receptor Alpha (TRα) and Beta (TRβ) Expression in Rat Primary Cerebellar Cell Cultures
Kiss DS, Ioja E, Toth I, Barany Z, Jocsak G, Bartha T, Horvath TL, Zsarnovszky A. Comparative Analysis of Zearalenone Effects on Thyroid Receptor Alpha (TRα) and Beta (TRβ) Expression in Rat Primary Cerebellar Cell Cultures. International Journal Of Molecular Sciences 2018, 19: 1440. PMID: 29751674, PMCID: PMC5983839, DOI: 10.3390/ijms19051440.Peer-Reviewed Original ResearchConceptsQuantitative reverse transcription polymerase chain reactionThyroid hormonesExpression levelsAbsence of gliaExpression of TRsReverse transcription-polymerase chain reactionThyroid receptor alphaTranscription-polymerase chain reactionPrimary cerebellar neuronsPrimary cerebellar granule cellsPrimary cerebellar cell culturesPostnatal brain developmentCerebellar granule cellsSerious health problemCerebellar cell culturesHormonal milieuGlial cellsBeta expressionGranule cellsReceptor alphaReceptor αThyroid receptor αHealth problemsLow dosesCerebellar neurons
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 ResearchHypothalamic TLR2 triggers sickness behavior via a microglia-neuronal axis
Jin S, Kim JG, Park JW, Koch M, Horvath TL, Lee BJ. Hypothalamic TLR2 triggers sickness behavior via a microglia-neuronal axis. Scientific Reports 2016, 6: 29424. PMID: 27405276, PMCID: PMC4942617, DOI: 10.1038/srep29424.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnorexiaArcuate Nucleus of HypothalamusCyclooxygenase InhibitorsEnergy MetabolismFeverInflammationLipopeptidesMaleMiceMice, KnockoutMicrogliaMyeloid Differentiation Factor 88NF-kappa BPro-OpiomelanocortinRatsReceptor, Melanocortin, Type 3Receptor, Melanocortin, Type 4Toll-Like Receptor 2Weight LossConceptsSickness behaviorHypothalamic inflammationToll-like receptor 2 (TLR2) activationSickness behavior symptomsNuclear factor kappa BBody weight lossReceptor 2 activationFactor kappa BNeuronal circuit functionHypothalamic microgliaProopiomelanocortin neuronsInflammatory mechanismsIntracerebroventricular injectionPathophysiologic mechanismsTLR2 activationInflammatory processCyclooxygenase pathwayNeuronal activationKappa BBehavior symptomsWeight lossInput organizationMicrogliaTLR2Inflammation
2015
Calcineurin Aγ is a Functional Phosphatase That Modulates Synaptic Vesicle Endocytosis*
Cottrell JR, Li B, Kyung JW, Ashford CJ, Mann JJ, Horvath TL, Ryan TA, Kim SH, Gerber DJ. Calcineurin Aγ is a Functional Phosphatase That Modulates Synaptic Vesicle Endocytosis*. Journal Of Biological Chemistry 2015, 291: 1948-1956. PMID: 26627835, PMCID: PMC4722470, DOI: 10.1074/jbc.m115.705319.Peer-Reviewed Original ResearchConceptsSynaptic vesicle cyclingVesicle cyclingHippocampal neuronsPsychiatric diseasesSynaptic vesicle endocytosisCultured rat hippocampal neuronsRNAi-mediated knockdownCalcineurin catalytic subunitRat hippocampal neuronsFunctional phosphataseCombination of immunocytochemistryVesicle endocytosisLow expression levelsCatalytic subunitPresynaptic substratePresynaptic terminalsPresynaptic functionΓ isoformsCalcineurin AαCatalytic isoformsImmuno-EMSpecific functionsExpression levelsMost tissuesPPP3CCEstrogen- and Satiety State-Dependent Metabolic Lateralization in the Hypothalamus of Female Rats
Toth I, Kiss DS, Jocsak G, Somogyi V, Toronyi E, Bartha T, Frenyo LV, Horvath TL, Zsarnovszky A. Estrogen- and Satiety State-Dependent Metabolic Lateralization in the Hypothalamus of Female Rats. PLOS ONE 2015, 10: e0137462. PMID: 26339901, PMCID: PMC4560379, DOI: 10.1371/journal.pone.0137462.Peer-Reviewed Original ResearchConceptsAd libitum fed animalsFemale ratsRight-sided dominanceSatiety stateFed animalsOvariectomized female ratsContribution of estrogenMetabolic differencesHours of fastingIntensity of cellsState 3 mitochondrial respirationHypothalamic functionMetabolic asymmetryTissue metabolismHypothalamusEstrogenProportion of animalsHypothalamic asymmetryRatsAd libitumLateralizationHigher centersMitochondrial respiration rateEnergy metabolism
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
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 regulatorReward Aspects of Gastrointestinal Hormones Mediated by Brain G Protein–Coupled Receptors
Koch M, Horvath TL. Reward Aspects of Gastrointestinal Hormones Mediated by Brain G Protein–Coupled Receptors. Biological Psychiatry 2012, 72: 340-342. PMID: 22872010, DOI: 10.1016/j.biopsych.2012.06.031.Peer-Reviewed Original Research
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 gainInflammationGhrelin-induced hypothermia: A physiological basis but no clinical risk
Wiedmer P, Strasser F, Horvath TL, Blum D, DiMarchi R, Lutz T, Schürmann A, Joost HG, Tschöp MH, Tong J. Ghrelin-induced hypothermia: A physiological basis but no clinical risk. Physiology & Behavior 2011, 105: 43-51. PMID: 21513721, PMCID: PMC3146973, DOI: 10.1016/j.physbeh.2011.03.027.Peer-Reviewed Original ResearchConceptsGhrelin treatmentBody temperatureApplication of ghrelinMedial preoptic areaPotential anatomical basisCold-sensitive neuronsGhrelin infusionBody core temperatureChronic i.Positive energy balanceGhrelin receptorPreoptic areaAxon terminalsClinical riskFood intakeGhrelinHealthy humansSerious hypothermiaMale subjectsPhysiologic circumstancesAnatomical basisHypothermiaCold exposureRelevant decreaseEnergy expenditureGhrelin Enhances Olfactory Sensitivity and Exploratory Sniffing in Rodents and Humans
Tong J, Mannea E, Aimé P, Pfluger PT, Yi CX, Castaneda TR, Davis HW, Ren X, Pixley S, Benoit S, Julliard K, Woods SC, Horvath TL, Sleeman MM, D'Alessio D, Obici S, Frank R, Tschöp MH. Ghrelin Enhances Olfactory Sensitivity and Exploratory Sniffing in Rodents and Humans. Journal Of Neuroscience 2011, 31: 5841-5846. PMID: 21490225, PMCID: PMC3089941, DOI: 10.1523/jneurosci.5680-10.2011.Peer-Reviewed Original ResearchConceptsExploratory sniffingAppetite-stimulating hormone ghrelinOlfactory sensitivityOverall functionGhrelin infusionIntracerebroventricular ghrelinGhrelin receptorHormone ghrelinSaline infusionOlfactory functionNeuroendocrine circuitsGhrelinUnderlying neural mechanismsEnergy homeostasisOdor detectionOlfactory processingOlfactory circuitFood seekingNeural mechanismsSniff magnitudeInfusionNovel roleOlfactory detectionSniffingSpecific effectsDifferential 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
2010
Estrogen Promotes Parvalbumin Expression in Arcuate Nucleus POMC Neurons
Sotonyi P, Gao Q, Bechmann I, Horvath TL. Estrogen Promotes Parvalbumin Expression in Arcuate Nucleus POMC Neurons. Reproductive Sciences 2010, 17: 1077-1080. PMID: 20713969, DOI: 10.1177/1933719110379651.Peer-Reviewed Original ResearchConceptsPOMC neuronsArcuate nucleus neuronsLean body massSuppression of feedingSuppress appetiteParvalbumin expressionEstrogen treatmentHypothalamic neuronsArcuate nucleusNeuronal degenerationNucleus neuronsFemale miceCalcium overloadExcitatory activityCalcium-binding proteinsCalcium influxReceptor presenceCalcium entrySustained satietyNeuronsEnergy expenditureEstradiolParvalbuminAppetiteBody massDirect 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