2022
AgRP neurons control feeding behaviour at cortical synapses via peripherally derived lysophospholipids
Endle H, Horta G, Stutz B, Muthuraman M, Tegeder I, Schreiber Y, Snodgrass IF, Gurke R, Liu ZW, Sestan-Pesa M, Radyushkin K, Streu N, Fan W, Baumgart J, Li Y, Kloss F, Groppa S, Opel N, Dannlowski U, Grabe HJ, Zipp F, Rácz B, Horvath TL, Nitsch R, Vogt J. AgRP neurons control feeding behaviour at cortical synapses via peripherally derived lysophospholipids. Nature Metabolism 2022, 4: 683-692. PMID: 35760867, PMCID: PMC9940119, DOI: 10.1038/s42255-022-00589-7.Peer-Reviewed Original ResearchConceptsFasting-induced hyperphagiaCortical excitabilityAgRP neuronsLysophosphatidic acidPeripheral metabolismHigher body mass indexFasting-induced elevationHypothalamic AgRP neuronsEffects of LPABody mass indexHigher cortical excitabilityBrain lipid levelsCentral nervous systemPrevalence of typeGlutamatergic transmissionHypothalamic agoutiMass indexOvernight fastingPeptide neuronsCortical synapsesLipid levelsFood intakeCerebrospinal fluidNervous systemPhospholipid levels
2021
Neuroinvasion of SARS-CoV-2 in human and mouse brain
Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, Iwasaki A. Neuroinvasion of SARS-CoV-2 in human and mouse brain. Journal Of Experimental Medicine 2021, 218: e20202135. PMID: 33433624, PMCID: PMC7808299, DOI: 10.1084/jem.20202135.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Central nervous systemSARS-CoV-2 neuroinvasionImmune cell infiltratesCOVID-19 patientsType I interferon responseMultiple organ systemsCOVID-19I interferon responseHuman brain organoidsNeuroinvasive capacityCNS infectionsCell infiltrateNeuronal infectionPathological featuresCortical neuronsRespiratory diseaseDirect infectionCerebrospinal fluidNervous systemMouse brainInterferon responseOrgan systemsHuman ACE2Infection
2016
Viral Spread to Enteric Neurons Links Genital HSV-1 Infection to Toxic Megacolon and Lethality
Khoury-Hanold W, Yordy B, Kong P, Kong Y, Ge W, Szigeti-Buck K, Ralevski A, Horvath TL, Iwasaki A. Viral Spread to Enteric Neurons Links Genital HSV-1 Infection to Toxic Megacolon and Lethality. Cell Host & Microbe 2016, 19: 788-799. PMID: 27281569, PMCID: PMC4902295, DOI: 10.1016/j.chom.2016.05.008.Peer-Reviewed Original ResearchConceptsGenital HSV-1 infectionEnteric nervous systemHSV-1 infectionSensory nervous systemNervous systemGenital herpesToxic megacolonHSV-1Genital mucosal epithelial cellsPeripheral sensory nervous systemDorsal root gangliaPathological inflammatory responsesMucosal epithelial cellsHerpes simplex virus 1Simplex virus 1Urinary retentionEnteric neuronsLaxative treatmentAutonomic gangliaRoot gangliaInflammatory responseViral gene transcriptionMouse modelInfectionEpithelial cellsMetabolism and Mental Illness
Sestan-Pesa M, Horvath TL. Metabolism and Mental Illness. Trends In Molecular Medicine 2016, 22: 174-183. PMID: 26776095, DOI: 10.1016/j.molmed.2015.12.003.Peer-Reviewed Original ResearchConceptsCentral nervous systemMental illnessBasic metabolic principlesHigher brain functionsCerebral cortexNovel therapiesNervous systemBrain functionSystemic controlPathological conditionsIllnessAppetiteCrucial regulatorFuture research strategiesOverwhelming evidenceMetabolic principlesFeeding behaviorMetabolismHypothalamusTherapyCortexBrain
2015
Hypothalamic Agrp Neurons Drive Stereotypic Behaviors beyond Feeding
Dietrich MO, Zimmer MR, Bober J, Horvath TL. Hypothalamic Agrp Neurons Drive Stereotypic Behaviors beyond Feeding. Cell 2015, 160: 1222-1232. PMID: 25748653, PMCID: PMC4484787, DOI: 10.1016/j.cell.2015.02.024.Peer-Reviewed Original ResearchConceptsHypothalamic AgRP neuronsAgRP neuronsNeuropeptidergic signalingReceptor signalingFunctional rolePotential therapeutic avenuesAgRP neuron activationStereotypic behaviorFeeding behaviorRepetitive behaviorsSignalingTherapeutic avenuesFood triggersAdult miceNervous systemDecreased anxietyNeuronsMinor effectActivationFood consumptionNeuron activationGoal-directed behaviorSensory informationFlexible goal-directed behaviorDisease
2013
Uncovering Novel Roles of Nonneuronal Cells in Body Weight Homeostasis and Obesity
Chowen JA, Argente J, Horvath TL. Uncovering Novel Roles of Nonneuronal Cells in Body Weight Homeostasis and Obesity. Endocrinology 2013, 154: 3001-3007. PMID: 23798599, PMCID: PMC3749483, DOI: 10.1210/en.2013-1303.Peer-Reviewed Original ResearchConceptsGlial cellsDiverse functionsNovel rolePhysiological functionsNumerous pathologiesPhysiological regulationNonneuronal cellsBody weight homeostasisCentral nervous systemSecondary complicationsWeight homeostasisCellsPathophysiological responsesSystemic metabolismMetabolic controlNervous systemVast lackPoor nutritionStructural supportNeuroendocrine researchObesityAreas of neuroscienceRecent advancesHeterogeneous classRoleHunger-promoting hypothalamic neurons modulate effector and regulatory T-cell responses
Matarese G, Procaccini C, Menale C, Kim JG, Kim JD, Diano S, Diano N, De Rosa V, Dietrich MO, Horvath TL. Hunger-promoting hypothalamic neurons modulate effector and regulatory T-cell responses. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 6193-6198. PMID: 23530205, PMCID: PMC3625304, DOI: 10.1073/pnas.1210644110.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAllelesAnimalsAntigensAutoimmunityCatalytic DomainEncephalomyelitis, Autoimmune, ExperimentalFlow CytometryFood DeprivationForkhead Transcription FactorsGenetic Predisposition to DiseaseHumansHungerHypothalamusInflammationMiceMice, KnockoutMice, TransgenicMyelin SheathNeuronsSirtuin 1T-Lymphocytes, RegulatoryThymus GlandConceptsRegulatory T cell responsesDelayed-type hypersensitivity responseHypothalamic feeding circuitsPeptide-expressing neuronsRegulatory T cellsSympathetic nervous systemT cell responsesForkhead box P3T helper 1Adaptive immune responsesWhole-body energy metabolismLow energy availabilityT cell activationAutoimmune disease susceptibilityBox P3Hypothalamic agoutiThymic generationHelper 1Hypersensitivity responseProinflammatory cytokinesHypothalamic neuronsSuppressive capacityT cellsImmune responseNervous system
2012
Ghrelin and the central regulation of feeding and energy balance
Abizaid A, Horvath TL. Ghrelin and the central regulation of feeding and energy balance. Indian Journal Of Endocrinology And Metabolism 2012, 16: 617-626. PMID: 23565498, PMCID: PMC3602992, DOI: 10.4103/2230-8210.105580.Peer-Reviewed Original Research
2011
Effects of chronic weight perturbation on energy homeostasis and brain structure in mice
Ravussin Y, Gutman R, Diano S, Shanabrough M, Borok E, Sarman B, Lehmann A, LeDuc CA, Rosenbaum M, Horvath TL, Leibel RL. Effects of chronic weight perturbation on energy homeostasis and brain structure in mice. AJP Regulatory Integrative And Comparative Physiology 2011, 300: r1352-r1362. PMID: 21411766, PMCID: PMC3119157, DOI: 10.1152/ajpregu.00429.2010.Peer-Reviewed Original ResearchConceptsDiet-induced obeseEnergy expenditureArcuate nucleus proopiomelanocortin neuronsWeight lossWeight-reduced individualsSustained weight lossReduced body weightObese human subjectsCentral nervous systemHuman subjectsSustained weight gainProopiomelanocortin neuronsBody massUpward resettingMale miceExcitatory synapsesBody fatMouse modelBody weightNervous systemSynaptic changesPersistent decreaseEnergy homeostasisWeight gainBrain structures
2009
Divergent Regulation of Energy Expenditure and Hepatic Glucose Production by Insulin Receptor in Agouti-Related Protein and POMC Neurons
Lin HV, Plum L, Ono H, Gutiérrez-Juárez R, Shanabrough M, Borok E, Horvath TL, Rossetti L, Accili D. Divergent Regulation of Energy Expenditure and Hepatic Glucose Production by Insulin Receptor in Agouti-Related Protein and POMC Neurons. Diabetes 2009, 59: 337-346. PMID: 19933998, PMCID: PMC2809966, DOI: 10.2337/db09-1303.Peer-Reviewed Original ResearchConceptsHepatic glucose productionAgRP neuronsPOMC neuronsInsulin receptorEnergy expenditureInsulin actionGlucose productionInhibitory synaptic contactsSulfonylurea receptor 1 (SUR1) subunitsCentral nervous systemL1 miceProopiomelanocortin neuronsHypothalamic insulinDivergent regulationInsulin resistanceSynaptic contactsInsulin suppressionGlucose metabolismHypothalamic deficiencyNervous systemLocomotor activityDecreased expressionEnergy homeostasisINSRNeurons
2008
N-acylphosphatidylethanolamine, a Gut- Derived Circulating Factor Induced by Fat Ingestion, Inhibits Food Intake
Gillum MP, Zhang D, Zhang XM, Erion DM, Jamison RA, Choi C, Dong J, Shanabrough M, Duenas HR, Frederick DW, Hsiao JJ, Horvath TL, Lo CM, Tso P, Cline GW, Shulman GI. N-acylphosphatidylethanolamine, a Gut- Derived Circulating Factor Induced by Fat Ingestion, Inhibits Food Intake. Cell 2008, 135: 813-824. PMID: 19041747, PMCID: PMC2643061, DOI: 10.1016/j.cell.2008.10.043.Peer-Reviewed Original ResearchConceptsFood intakeInhibits food intakeTreatment of obesityNovel therapeutic targetCentral nervous systemUnknown physiological significanceFat ingestionCirculating factorsN-acylphosphatidylethanolaminePlasma lipidsIntracerebroventricular infusionPhysiologic dosesSystemic administrationTherapeutic targetBody weightNervous systemIngested fatSmall intestineIntakeTaste aversionInfusionPhysiological significanceNanomolar amountsObesityHypothalamus
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 handlingMiceWakefulness
2006
The unfolding cannabinoid story on energy homeostasis: central or peripheral site of action?
Horvath TL. The unfolding cannabinoid story on energy homeostasis: central or peripheral site of action? International Journal Of Obesity 2006, 30: s30-s32. PMID: 16570102, DOI: 10.1038/sj.ijo.0803275.Peer-Reviewed Original ResearchConceptsBlood-brain barrierCB1 receptor antagonistCentral endocannabinoid systemBody weight regulationWhite adipose tissueCentral nervous systemMesolimbic reward circuitryObserved beneficial effectsEnergy metabolism regulationAnorectic effectPeripheral actionsReceptor antagonistEndocannabinoid systemCB1 antagonistCB1 receptorsBrain sitesCannabinoid actionFood intakeHuman trialsPeripheral tissuesMetabolic disordersWeight regulationAdipose tissueNervous systemPharmaceutical approachesRetinopetal Axons in Mammals: Emphasis on Histamine and Serotonin
Gastinger MJ, Tian N, Horvath T, Marshak DW. Retinopetal Axons in Mammals: Emphasis on Histamine and Serotonin. Current Eye Research 2006, 31: 655-667. PMID: 16877274, PMCID: PMC3351198, DOI: 10.1080/02713680600776119.Peer-Reviewed Original ResearchConceptsRetinopetal axonsEffects of serotoninCentral nervous systemRetina of mammalsDorsal rapheHistaminergic neuronsOptic nervePosterior hypothalamusInner retinaBrain stemRetinal neuronsNervous systemRetinal diseasesAxonsArousal systemNeuronsHistamineAnatomical studyRetinaPerikaryaSerotoninNerveHypothalamusEtiologyRaphe
2003
Mitochondrial uncoupling protein 2 in the central nervous system: neuromodulator and neuroprotector
Horvath TL, Diano S, Barnstable C. Mitochondrial uncoupling protein 2 in the central nervous system: neuromodulator and neuroprotector. Biochemical Pharmacology 2003, 65: 1917-1921. PMID: 12787871, DOI: 10.1016/s0006-2952(03)00143-6.Peer-Reviewed Original ResearchConceptsMitochondrial membrane potentialInner membraneRole of UCP2Normal neuronal functionDiverse tissuesUnknown functionProtein 2Functional significanceImportant playersCentral nervous systemNeuronal functionProteinMembrane potentialNervous systemUCP2Disease statesUCPBrown adipose tissueNew avenuesMitochondriaTissueAdipose tissueUCP1Better understandingUncouplerEstradiol 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
2002
Uncoupling 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
1998
Leptin 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 localization
1996
Aromatase Immunoreactivity in Axon Terminals of the Vertebrate Brain
Naftolin F, Horvath T, Jakab R, Leranth C, Harada N, Balthazart J. Aromatase Immunoreactivity in Axon Terminals of the Vertebrate Brain. Neuroendocrinology 1996, 63: 149-155. PMID: 9053779, DOI: 10.1159/000126951.Peer-Reviewed Original ResearchConceptsAxon terminalsAromatase immunoreactivityAxonal processesDifferent vertebrate speciesAdult central nervous systemRole of aromataseSmall clear synaptic vesiclesCentral nervous systemClear synaptic vesiclesVertebrate speciesSubcellular locationMost vertebratesSpecific limbicNeuronal perikaryaAromatase activityElectron microscopic examinationEstrogen synthesisHypothalamic structuresSubcellular distributionSynaptic levelVertebrate brainNervous systemBrain aromataseMolecular biologyIntraneuronal production
1992
Presence of calbindin and lack of parvalbumin in progesterone receptor-containing neurons of the monkey mediobasal hypothalamus
Horvath TL, Leranth C, Naftolin* F. Presence of calbindin and lack of parvalbumin in progesterone receptor-containing neurons of the monkey mediobasal hypothalamus. Neuroscience 1992, 50: 309-314. PMID: 1436493, DOI: 10.1016/0306-4522(92)90425-2.Peer-Reviewed Original ResearchConceptsProgesterone receptor-containing neuronsReceptor-containing neuronsReceptor-containing cellsCalbindin-immunoreactive neuronsProgesterone receptorAsymmetric synaptic contactsPresence of calbindinCentral nervous systemAfrican green monkeysLight microscopic resultsGABA neuronsGABAergic neuronsPeriventricular areaSynaptic contactsMonkey hypothalamusPostsynaptic targetsExcitatory fibresInfundibular nucleusMediobasal hypothalamusCalcium-binding proteinsNervous systemCalbindin cellsCalbindinNeuronsParvalbumin content