2017
Molecular and Epigenetic Mechanisms for the Complex Effects of Stress on Synaptic Physiology and Cognitive Functions
Yuen EY, Wei J, Yan Z. Molecular and Epigenetic Mechanisms for the Complex Effects of Stress on Synaptic Physiology and Cognitive Functions. The International Journal Of Neuropsychopharmacology 2017, 20: 948-955. PMID: 29016816, PMCID: PMC5737802, DOI: 10.1093/ijnp/pyx052.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCognition DisordersEpigenesis, GeneticGlutamic AcidHumansStress, PsychologicalSynapsesSynaptic TransmissionConceptsEpigenetic mechanismsReceptor membrane traffickingStress-induced regulationSynaptic physiologyMembrane traffickingEpigenetic controlCytoskeleton networkGene expressionKey moleculesComplex effectsStress-related mental disordersPresynaptic glutamate releaseExcitatory synaptic transmissionStress-induced modulationPhysiologyGlutamatergic transmissionGlutamate releaseSynaptic transmissionBiphasic effectAnimal studiesComplex changesMental disordersBrain regionsChronic stressStress hormones
2014
Synergistic Regulation of Glutamatergic Transmission by Serotonin and Norepinephrine Reuptake Inhibitors in Prefrontal Cortical Neurons*
Yuen EY, Qin L, Wei J, Liu W, Liu A, Yan Z. Synergistic Regulation of Glutamatergic Transmission by Serotonin and Norepinephrine Reuptake Inhibitors in Prefrontal Cortical Neurons*. Journal Of Biological Chemistry 2014, 289: 25177-25185. PMID: 25056951, PMCID: PMC4155681, DOI: 10.1074/jbc.m114.567610.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic Uptake InhibitorsAnimalsBicucullineBlotting, WesternCarrier ProteinsCells, CulturedDesipramineDrug SynergismDynaminsEndocytosisExcitatory Postsynaptic PotentialsFluoxetineP38 Mitogen-Activated Protein KinasesPatch-Clamp TechniquesPrefrontal CortexPyramidal CellsRab5 GTP-Binding ProteinsRatsReceptor, Serotonin, 5-HT1AReceptors, Adrenergic, alpha-2Receptors, AMPASelective Serotonin Reuptake InhibitorsSignal TransductionSynaptic TransmissionConceptsNorepinephrine reuptake inhibitorsExcitatory postsynaptic currentsΑ2-adrenergic receptorsReuptake inhibitorsGlutamatergic transmissionPostsynaptic currentsCortical neuronsAMPAR-mediated excitatory postsynaptic currentsG proteinsPrefrontal cortex pyramidal neuronsDynamin-mediated endocytosisSelective reuptake inhibitorsProtein α subunitsCortex pyramidal neuronsPrefrontal cortical neuronsP38 kinase activityAMPAR surface expressionGood therapeutic effectG-protein modulatorsPyramidal neuronsClinical studiesTherapeutic effectMonoamine systemsAMPA receptorsKinase activityMemory Enhancement by Targeting Cdk5 Regulation of NR2B
Plattner F, Hernández A, Kistler TM, Pozo K, Zhong P, Yuen EY, Tan C, Hawasli AH, Cooke SF, Nishi A, Guo A, Wiederhold T, Yan Z, Bibb JA. Memory Enhancement by Targeting Cdk5 Regulation of NR2B. Neuron 2014, 81: 1070-1083. PMID: 24607229, PMCID: PMC4010123, DOI: 10.1016/j.neuron.2014.01.022.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCells, CulturedCyclin-Dependent Kinase 5FemaleHippocampusMaleMemoryMemory DisordersMiceMice, Inbred C57BLMice, KnockoutMolecular Sequence DataNeuronal PlasticityNeuronsOrgan Culture TechniquesPhosphorylationRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateSynaptic TransmissionConceptsCell surface expressionReceptor cell surface expressionCyclin-dependent kinase 5Cdk5 regulationN-methyl-D-aspartate receptorsRegulatory mechanismsKinase 5NR2B functionSurface expressionNMDAR functionSubunit NR2BSynaptic plasticityEnhancerFundamental roleRegulationMemory formationNMDAR subunit NR2BCognitive enhancersValid treatment strategyPrime targetSynaptic transmissionNR2B phosphorylationNR2BPhosphorylationSurface level
2013
Restoration of Glutamatergic Transmission by Dopamine D4 Receptors in Stressed Animals*
Yuen EY, Zhong P, Li X, Wei J, Yan Z. Restoration of Glutamatergic Transmission by Dopamine D4 Receptors in Stressed Animals*. Journal Of Biological Chemistry 2013, 288: 26112-26120. PMID: 23884421, PMCID: PMC3764814, DOI: 10.1074/jbc.m112.396648.Peer-Reviewed Original ResearchConceptsD4 receptorsDopamine D4 receptorExcitatory transmissionGlutamatergic transmissionPrefrontal cortexAMPA receptor-mediated synaptic transmissionReceptor-mediated synaptic transmissionCalcium/calmodulin kinase II activityEffects of D4PFC pyramidal neuronsCalmodulin kinase II activityKey brain regionsAttention deficit hyperactivity disorderBi-directional regulationDeficit hyperactivity disorderPyramidal neuronsCortical excitabilityDopaminergic inputSynaptic actionsSynaptic transmissionPotent reductionAMPA receptorsKinase II activityStressed animalsMaladaptive changesEstrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and cognition
Wei J, Yuen EY, Liu W, Li X, Zhong P, Karatsoreos IN, McEwen BS, Yan Z. Estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and cognition. Molecular Psychiatry 2013, 19: 588-598. PMID: 23835908, DOI: 10.1038/mp.2013.83.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAromataseAromatase InhibitorsCognitionEstradiolEstrogensFemaleGlutamic AcidMaleMemory DisordersPrefrontal CortexPyramidal CellsRats, Sprague-DawleyReceptors, EstrogenReceptors, GlutamateRecognition, PsychologyRNA, MessengerSex CharacteristicsStress, PsychologicalSynaptic TransmissionConceptsTemporal order recognition memoryGlutamatergic transmissionPrefrontal cortexStressed malesPFC of femalesNormal glutamatergic transmissionGlutamate receptor surface expressionPFC pyramidal neuronsYoung female ratsAdministration of estradiolLevels of aromatasePFC-dependent cognitionReceptor surface expressionBiosynthesis of estrogensEstrogen protectsPyramidal neuronsGlutamatergic deficitsRestraint stressFemale ratsEstrogen receptorGlutamate receptorsDetrimental effectsDimorphic effectsMemory impairmentStressed females
2012
Disrupted GABAAR trafficking and synaptic inhibition in a mouse model of Huntington's disease
Yuen EY, Wei J, Zhong P, Yan Z. Disrupted GABAAR trafficking and synaptic inhibition in a mouse model of Huntington's disease. Neurobiology Of Disease 2012, 46: 497-502. PMID: 22402331, PMCID: PMC3323696, DOI: 10.1016/j.nbd.2012.02.015.Peer-Reviewed Original ResearchConceptsHuntingtin associated protein 1Mouse modelHuntington's diseaseSynaptic inhibitionExcitatory/inhibitory balanceInhibitory synaptic efficacyDiminished surface expressionNeurodegenerative movement disorderTransgenic mouse modelHD mouse modelsNeuronal excitotoxicityInhibitory balanceMovement disordersAssociated protein 1Synaptic transmissionGABAAR traffickingSynaptic efficacySynaptic functionDiseaseReceptorsMutant huntingtinProtein 1Protein 5Surface expressionPolyglutamine repeats
2011
The Novel Antipsychotic Drug Lurasidone Enhances N-Methyl-d-aspartate Receptor-Mediated Synaptic Responses
Yuen EY, Li X, Wei J, Horiguchi M, Meltzer HY, Yan Z. The Novel Antipsychotic Drug Lurasidone Enhances N-Methyl-d-aspartate Receptor-Mediated Synaptic Responses. Molecular Pharmacology 2011, 81: 113-119. PMID: 22072817, PMCID: PMC3263951, DOI: 10.1124/mol.111.076141.Peer-Reviewed Original ResearchConceptsAtypical antipsychotic drugsEffect of lurasidoneSynaptic responsesVivo administrationN-methyl-D-aspartate (NMDA) receptor hypofunctionShort-term administrationCortical pyramidal neuronsAtypical APDsReceptor antagonist haloperidolAtypical APD clozapineKey molecular targetsSubchronic administrationPyramidal neuronsReceptor hypofunctionReceptor antagonismReceptor antagonistAntagonist haloperidolNMDAR responsesNMDAR synaptic functionAntipsychotic drugsNR2B subunitSerotonin 5Noncompetitive antagonistLurasidoneCognitive impairmentImpaired α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) Receptor Trafficking and Function by Mutant Huntingtin*
Mandal M, Wei J, Zhong P, Cheng J, Duffney L, Liu W, Yuen E, Twelvetrees A, Li S, Li X, Kittler J, Yan Z. Impaired α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) Receptor Trafficking and Function by Mutant Huntingtin*. Journal Of Biological Chemistry 2011, 286: 33719-33728. PMID: 21832090, PMCID: PMC3190808, DOI: 10.1074/jbc.m111.236521.Peer-Reviewed Original ResearchConceptsMiniature excitatory postsynaptic currentsMouse modelMutant huntingtinAMPAR-mediated synaptic transmissionHuntington Disease PathophysiologyAMPAR-mediated miniature excitatory postsynaptic currentsExcitatory postsynaptic currentsTransgenic mouse modelHD mouse modelsIsoxazolepropionic acid receptor (AMPAR) traffickingReceptor traffickingAMPA receptor traffickingPolyQ-httGlutamatergic transmissionPostsynaptic currentsSynaptic excitationSynaptic transmissionAMPA receptorsWild-type huntingtinNeuronal culturesDisease pathophysiologySynaptic functionAMPAR traffickingΑ-aminoDiminished strength
2010
Homeostatic regulation of glutamatergic transmission by dopamine D4 receptors
Yuen EY, Zhong P, Yan Z. Homeostatic regulation of glutamatergic transmission by dopamine D4 receptors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 22308-22313. PMID: 21135234, PMCID: PMC3009820, DOI: 10.1073/pnas.1010025108.Peer-Reviewed Original ResearchConceptsSynaptic transmissionPrefrontal cortex pyramidal neuronsCortex pyramidal neuronsExcitatory synaptic transmissionAttention deficit hyperactivity disorderRole of dopamineDopamine D4 receptorGlutamatergic transmissionPyramidal neuronsCortical excitabilityProfound depressionMental disordersSynaptic functionBrain regionsD4 receptorsSynaptic factorsAMPAR traffickingPrefrontal cortexDistinct signaling pathwaysHyperactivity disorderCaMKII activityBidirectional regulationHomeostatic regulationReceptorsSignaling pathwaysRegulation of AMPA receptor channels and synaptic plasticity by cofilin phosphatase Slingshot in cortical neurons
Yuen EY, Liu W, Kafri T, Van Praag H, Yan Z. Regulation of AMPA receptor channels and synaptic plasticity by cofilin phosphatase Slingshot in cortical neurons. The Journal Of Physiology 2010, 588: 2361-2371. PMID: 20442266, PMCID: PMC2915513, DOI: 10.1113/jphysiol.2009.186353.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCells, CulturedCerebral CortexCofilin 1ElectrophysiologyExcitatory Postsynaptic PotentialsImmunohistochemistryLentivirusMicrofilament ProteinsNeuronal PlasticityNeuronsPhosphoric Monoester HydrolasesRatsReceptors, AMPARNA, Small InterferingRNA, ViralSynapsesSynaptic TransmissionConceptsExcitatory postsynaptic currentsCortical neuronsSynaptic transmissionSynaptic plasticityReceptor-mediated excitatory postsynaptic currentsAMPA receptor-mediated excitatory postsynaptic currentsPhosphatase SlingshotActin dynamicsAMPA receptor channelsFunction-blocking antibodiesSmall RNA interferenceAMPAR EPSCsMajor actin depolymerizing factorPostsynaptic currentsCofilin phosphatase SlingshotGluR-1Synaptic functionActin depolymerizing factorSpine morphologyAMPAR traffickingReceptor channelsActin cytoskeletonRNA interferenceNeuronsCofilin activationMechanisms for acute stress-induced enhancement of glutamatergic transmission and working memory
Yuen EY, Liu W, Karatsoreos IN, Ren Y, Feng J, McEwen BS, Yan Z. Mechanisms for acute stress-induced enhancement of glutamatergic transmission and working memory. Molecular Psychiatry 2010, 16: 156-170. PMID: 20458323, PMCID: PMC3108461, DOI: 10.1038/mp.2010.50.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBiophysicsCells, CulturedCorticosteroneDose-Response Relationship, DrugDrug InteractionsElectric StimulationExcitatory Amino Acid AgentsExcitatory Postsynaptic PotentialsGene Expression RegulationGlutamic AcidGreen Fluorescent ProteinsHormone AntagonistsImmediate-Early ProteinsIn Vitro TechniquesLong-Term PotentiationMaleMaze LearningMemory, Short-TermMifepristonePatch-Clamp TechniquesPeptidesPrefrontal CortexProtein Serine-Threonine KinasesPyramidal CellsRab GTP-Binding ProteinsRatsRats, Sprague-DawleyReceptors, GlutamateRNA, Small InterferingStress, PsychologicalSynaptic TransmissionTime FactorsTransfectionConceptsPrefrontal cortexGlutamatergic transmissionAcid receptorsPFC pyramidal neuronsAspartic acid (NMDA) receptorsIsoxazolepropionic acid (AMPA) receptorsInduction of serumCorticosteroid stress hormonesFunction of NMDARsStress-induced enhancementSustained potentiationPyramidal neuronsCorticosterone treatmentSynaptic responsesSynaptic transmissionBehavioral stressorsGlucocorticoid-inducible kinaseGlucocorticoid receptorAcute stressStress hormonesΑ-aminoSurface expressionReceptorsUnderlying mechanismReceptor recyclingDelivery of GABAARs to Synapses Is Mediated by HAP1-KIF5 and Disrupted by Mutant Huntingtin
Twelvetrees A, Yuen E, Arancibia-Carcamo I, MacAskill A, Rostaing P, Lumb M, Humbert S, Triller A, Saudou F, Yan Z, Kittler J. Delivery of GABAARs to Synapses Is Mediated by HAP1-KIF5 and Disrupted by Mutant Huntingtin. Neuron 2010, 65: 53-65. PMID: 20152113, PMCID: PMC2841506, DOI: 10.1016/j.neuron.2009.12.007.Peer-Reviewed Original ResearchConceptsHuntingtin-associated protein 1Huntington's diseaseInhibitory postsynaptic currentsMutant huntingtinInhibitory synaptic currentsBrain excitabilityPostsynaptic currentsSynaptic inhibitionTherapeutic approachesSynaptic currentsDiseaseBrain information processingMolecular targetsSynapsesProtein 1Protein 5Protein huntingtinHuntingtinReceptorsPolyglutamine repeatsInhibitionGABAARsExcitability
2009
Dopamine D4 Receptors Regulate AMPA Receptor Trafficking and Glutamatergic Transmission in GABAergic Interneurons of Prefrontal Cortex
Yuen EY, Yan Z. Dopamine D4 Receptors Regulate AMPA Receptor Trafficking and Glutamatergic Transmission in GABAergic Interneurons of Prefrontal Cortex. Journal Of Neuroscience 2009, 29: 550-562. PMID: 19144855, PMCID: PMC2768380, DOI: 10.1523/jneurosci.5050-08.2009.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsCalcineurinColchicineDopamine AgentsEnzyme InhibitorsGamma-Aminobutyric AcidGlutamate DecarboxylaseGlutamic AcidGreen Fluorescent ProteinsIn Vitro TechniquesInterneuronsMiceMice, TransgenicMicrofilament ProteinsPatch-Clamp TechniquesPhalloidinePhosphoric Monoester HydrolasesPrefrontal CortexProtein TransportRatsReceptors, AMPAReceptors, Dopamine D4RNA, Small InterferingSynaptic TransmissionTransfectionTubulin ModulatorsConceptsGABAergic interneuronsAttention deficit hyperactivity disorderGABAergic inhibitionGlutamatergic transmissionPrefrontal cortexAMPAR-mediated synaptic transmissionLocal circuit neuronsPFC pyramidal neuronsExcitatory synaptic strengthAbnormal neural synchronyAMPA receptor traffickingDopamine D4 receptorAMPAR EPSCsDeficit hyperactivity disorderPFC interneuronsPyramidal neuronsMajor actin depolymerizing factorMemory disturbanceSynaptic transmissionAMPA receptorsCortical circuitsNeuronal activityPersistent suppressionInterneuronsMental disorders
2007
Calpain regulation of AMPA receptor channels in cortical pyramidal neurons
Yuen EY, Gu Z, Yan Z. Calpain regulation of AMPA receptor channels in cortical pyramidal neurons. The Journal Of Physiology 2007, 580: 241-254. PMID: 17234699, PMCID: PMC2075435, DOI: 10.1113/jphysiol.2006.122754.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCalpainCells, CulturedCerebral CortexElectrophysiologyEndocytosisGerbillinaeImmunohistochemistryMaleMAP Kinase Kinase 2NeuronsNeuroprotective AgentsPatch-Clamp TechniquesPyramidal CellsRatsRats, Sprague-DawleyReceptors, AMPAReceptors, Cell SurfaceReceptors, N-Methyl-D-AspartateStimulation, ChemicalSynapsesSynaptic TransmissionConceptsCortical pyramidal neuronsNMDA receptorsPyramidal neuronsAMPA receptorsNMDA treatmentCalpain inhibitorsIschaemia-induced depressionFast excitatory synaptic transmissionTransient ischemic insultAMPAR-mediated currentsExcitatory synaptic transmissionCalpain-dependent mannerAMPA receptor channelsSelective calpain inhibitorsExcitotoxic conditionsIschemic animalsIschemic insultNeuronal excitotoxicityAMPAR currentsAMPA responsesCortical culturesExtracellular glutamateGlutamate receptorsGlutamate triggersNeuronal excitability