2016
Hypothalamic 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
2010
Corticosterone Regulates Synaptic Input Organization of POMC and NPY/AgRP Neurons in Adult Mice
Gyengesi E, Liu ZW, D'Agostino G, Gan G, Horvath TL, Gao XB, Diano S. Corticosterone Regulates Synaptic Input Organization of POMC and NPY/AgRP Neurons in Adult Mice. Endocrinology 2010, 151: 5395-5402. PMID: 20843996, PMCID: PMC2954711, DOI: 10.1210/en.2010-0681.Peer-Reviewed Original ResearchConceptsNPY/AgRP neuronsSynaptic input organizationSham-operated controlsAgRP neuronsADX miceCorticosterone replacementNeuropeptide YArcuate nucleusSynaptic arrangementsInput organizationPair-fed control animalsPutative excitatory synapsesPutative inhibitory synapsesHypothalamic arcuate nucleusEffects of adrenalectomySham-operated animalsNumber of synapsesPOMC neuronsProtein (AgRP) neuronsOrexigenic actionMembrane potentialSynaptic analysisInhibitory synapsesExcitatory synapsesFood intakeSynaptic 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 expenditureAdiposityGhrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite
Abizaid A, Liu ZW, Andrews ZB, Shanabrough M, Borok E, Elsworth JD, Roth RH, Sleeman MW, Picciotto MR, Tschöp MH, Gao XB, Horvath TL. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. Journal Of Clinical Investigation 2006, 116: 3229-3239. PMID: 17060947, PMCID: PMC1618869, DOI: 10.1172/jci29867.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAppetiteDopamineFluorescent Antibody TechniqueGhrelinMaleMesencephalonMiceMice, Inbred C57BLMice, KnockoutNeuronsNucleus AccumbensPatch-Clamp TechniquesPeptide HormonesRatsRats, Sprague-DawleyReceptors, GhrelinReceptors, G-Protein-CoupledTime FactorsVentral Tegmental AreaConceptsVentral tegmental areaGHSR-deficient miceGHSR-dependent mannerGut hormone ghrelinDopamine neuronal activityMidbrain dopamine neuronsMesolimbic reward circuitrySynaptic input organizationPeripheral ghrelinRebound feedingVTA administrationOrexigenic effectDopamine turnoverGHSR antagonistDopamine neuronsHypothalamic centersTegmental areaHormone ghrelinNucleus accumbensGhrelinNeuronal activitySynapse formationReward circuitryInput organizationFeeding schedule
2005
Input organization and plasticity of hypocretin neurons Possible clues to obesity’s association with insomnia
Horvath TL, Gao XB. Input organization and plasticity of hypocretin neurons Possible clues to obesity’s association with insomnia. Cell Metabolism 2005, 1: 279-286. PMID: 16054072, DOI: 10.1016/j.cmet.2005.03.003.Peer-Reviewed Original ResearchConceptsHypocretin neuronsSynaptic currentsHypothalamic hypocretin neuronsMore excitatory synapsesOvernight food deprivationElevated food intakeExcitatory synaptic currentsControl of arousalCause of narcolepsyStress-induced plasticityHypocretin levelsLeptin administrationHypocretin cellsHypocretin signalingMetabolic disturbancesObesity associationSynaptic organizationExcitatory synapsesFood intakeInhibitory inputsCell bodiesUnderlying causeNeuronsInput organizationFood deprivation