2023
A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model
Lv H, Catarino J, Li D, Liu B, Gao X, Horvath T, Huang Y. A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2300015120. PMID: 37036983, PMCID: PMC10120042, DOI: 10.1073/pnas.2300015120.Peer-Reviewed Original ResearchConceptsVesicular GABA transporterActivity-based anorexiaExpression of AgRPNeuropeptide YAgRP neuronsAnorexia nervosaAnxiety/depressive-like behaviorsHypothalamic AgRP neuronsDepressive-like behaviorCurrent treatment optionsHigh relapse rateStress-related disordersHuman neuronal cellsNutritional supportRelapse rateTreatment optionsAnxiolytic effectsPsychiatric illnessMouse modelAnimal modelsHigh mortalityGABA transporterGenetic ablationNeuronal cellsNeurons
2020
Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice
Tan Y, Hang F, Liu ZW, Stoiljkovic M, Wu M, Tu Y, Han W, Lee AM, Kelley C, Hajos M, Lu L, de Lecea L, de Araujo I, Picciotto M, Horvath TL, Gao XB. Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice. Journal Of Clinical Investigation 2020, 130: 4985-4998. PMID: 32516139, PMCID: PMC7456212, DOI: 10.1172/jci130889.Peer-Reviewed Original ResearchConceptsHcrt cellsObese miceDiet-induced obese miceObese male miceExcessive energy intakeNeuropeptide hypocretin/orexinHypocretin/orexinHcrt neuronsMale miceHcrt systemClinical studiesCommon causeSynaptic transmissionObese animalsEnergy intakeAcute stressCognitive functionSalient stimuliAlters responsesExact mechanismMiceHomeostatic regulationNeuronal networksBehavioral changesNeurons
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
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
2002
Hypocretin/Orexin Excites Hypocretin Neurons via a Local Glutamate Neuron—A Potential Mechanism for Orchestrating the Hypothalamic Arousal System
Li Y, Gao X, Sakurai T, van den Pol AN. Hypocretin/Orexin Excites Hypocretin Neurons via a Local Glutamate Neuron—A Potential Mechanism for Orchestrating the Hypothalamic Arousal System. Neuron 2002, 36: 1169-1181. PMID: 12495630, DOI: 10.1016/s0896-6273(02)01132-7.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsArousalCarrier ProteinsExcitatory Amino Acid AgonistsFeedbackGABA AgonistsGamma-Aminobutyric AcidGenes, ReporterGlutamic AcidGreen Fluorescent ProteinsHypothalamusImmunohistochemistryIntracellular Signaling Peptides and ProteinsLuminescent ProteinsMiceMice, TransgenicNeural InhibitionNeural PathwaysNeuronsNeuropeptidesOrexinsPresynaptic TerminalsSodium Channel BlockersSynaptic TransmissionConceptsHypothalamic arousal systemsHypocretin neuronsArousal systemSpike frequencyLocal glutamatergic neuronsMouse brain slicesGlutamate releaseGlutamatergic neuronsHypocretin-1Hypocretin cellsPresynaptic facilitationBrain slicesNeuron activityOutward currentsEnergy homeostasisModulates sleepNeuronsPotential mechanismsDirect effectPossible mechanismCellsNarcolepsyHypocretinNorepinephrineAcetylcholine
2001
GABA, Not Glutamate, a Primary Transmitter Driving Action Potentials in Developing Hypothalamic Neurons
Gao X, Van Den Pol A. GABA, Not Glutamate, a Primary Transmitter Driving Action Potentials in Developing Hypothalamic Neurons. Journal Of Neurophysiology 2001, 85: 425-434. PMID: 11152743, DOI: 10.1152/jn.2001.85.1.425.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsBicucullineCells, CulturedChloridesExcitatory Amino Acid AntagonistsGABA-A Receptor AntagonistsGamma-Aminobutyric AcidGlutamic AcidGramicidinHypothalamusImmunohistochemistryIn Vitro TechniquesMiceNeuronsNeurotransmitter AgentsPatch-Clamp TechniquesReceptors, GlutamateSpinal CordConceptsHypothalamic neuronsReceptor antagonist bicucullinePrimary inhibitory neurotransmitterMouse hypothalamic neuronsPrimary excitatory transmitterAntagonist bicucullineExcitatory transmitterGABA circuitsGlutamate transmissionInhibitory neurotransmitterMature brainBrain slicesSynaptic releaseNeuronal activitySpike activityNeuronal connectionsSpike frequencyExtracellular recordingsAction potentialsAntagonist 2Brain developmentHebbian mechanismsIntracellular ClNeuronsGABA
2000
GABA release from mouse axonal growth cones
Gao X, van den Pol A. GABA release from mouse axonal growth cones. The Journal Of Physiology 2000, 523: 629-637. PMID: 10718743, PMCID: PMC2269824, DOI: 10.1111/j.1469-7793.2000.t01-1-00629.x.Peer-Reviewed Original ResearchConceptsGABA releaseSynapse formationGrowth conesSpontaneous GABA releaseAxonal growth conesHypothalamic neuronsTransmitter phenotypeAxon terminalsNeurotransmitter receptorsTransgenic miceAction potentialsGABAProtein kinase C activityNeuronal membranesAxonsNeuronal developmentGreen fluorescent proteinKinase C activityNeuronsVesicular mechanismPKC activationFluorescent proteinC activityLow levelsRelease
1999
Kainate Acts at Presynaptic Receptors to Increase GABA Release From Hypothalamic Neurons
Liu Q, Patrylo P, Gao X, van den Pol A. Kainate Acts at Presynaptic Receptors to Increase GABA Release From Hypothalamic Neurons. Journal Of Neurophysiology 1999, 82: 1059-1062. PMID: 10444697, DOI: 10.1152/jn.1999.82.2.1059.Peer-Reviewed Original Research
1998
GABA-Dependent Firing of Glutamate-Evoked Action Potentials at AMPA/Kainate Receptors in Developing Hypothalamic Neurons
Gao X, Chen G, van den Pol A. GABA-Dependent Firing of Glutamate-Evoked Action Potentials at AMPA/Kainate Receptors in Developing Hypothalamic Neurons. Journal Of Neurophysiology 1998, 79: 716-726. PMID: 9463435, DOI: 10.1152/jn.1998.79.2.716.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidAction potentialsHypothalamic neuronsAMPA/kainate receptorsN-methyl-D-aspartate receptorsGlutamate-mediated excitationAdult mammalian CNSFire action potentialsMajor inhibitory roleExcitatory functionGlutamate responseGlutamate receptorsKainate receptorsMammalian CNSMaximal effectSlight temporal delayNeuronal circuitsInhibitory roleNeuronsReceptorsBroad time windowDepolarizationGlutamatePresent studySimilar resultsThe hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity
de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg E, Gautvik VT, Bartlett FS, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG. The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 322-327. PMID: 9419374, PMCID: PMC18213, DOI: 10.1073/pnas.95.1.322.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCarrier ProteinsChromosomesConsensus SequenceHomeostasisHypothalamus, PosteriorIntracellular Signaling Peptides and ProteinsMaleMiceMolecular Sequence DataNeuronsNeuropeptidesNeurotransmitter AgentsOrexinsProtein PrecursorsRatsRats, WistarSecretinSynaptic VesiclesConceptsGut hormone secretinLateral hypothalamic areaNeuronal cell bodiesLarge granular vesiclesPosterior hypothalamusHypothalamic areaHypothalamic neuronsHippocampal neuronsCell bodiesGranular vesiclesHcrt peptidesHormone secretinNeuronsHypocretinNeuroexcitatory activityPeptidesPutative precursorBrainstemThalamusHypothalamusImmunoreactivityCNSNeurotransmittersSecretinProtein products