Featured Publications
Epigenetic Mechanisms of Serotonin Signaling
Holloway T, González-Maeso J. Epigenetic Mechanisms of Serotonin Signaling. ACS Chemical Neuroscience 2015, 6: 1099-1109. PMID: 25734378, PMCID: PMC4838281, DOI: 10.1021/acschemneuro.5b00033.Peer-Reviewed Original ResearchConceptsEpigenetic mechanismsHeritable epigenetic modificationsNumerous physiological responsesSignal transduction mechanismsReceptor-dependent signalingEpigenetic marksHistone modificationsGene functionEpigenetic modificationsDNA methylationCellular phenotypesGene expressionTransduction mechanismsPhysiological responsesFundamental roleDiverse setComplex interactionsCentral nervous systemRecent advancesFundamental questionsIntense researchMethylationNervous systemSignalingMechanismPrenatal Stress Induces Schizophrenia-Like Alterations of Serotonin 2A and Metabotropic Glutamate 2 Receptors in the Adult Offspring: Role of Maternal Immune System
Holloway T, Moreno JL, Umali A, Rayannavar V, Hodes GE, Russo SJ, González-Maeso J. Prenatal Stress Induces Schizophrenia-Like Alterations of Serotonin 2A and Metabotropic Glutamate 2 Receptors in the Adult Offspring: Role of Maternal Immune System. Journal Of Neuroscience 2013, 33: 1088-1098. PMID: 23325246, PMCID: PMC3711555, DOI: 10.1523/jneurosci.2331-12.2013.Peer-Reviewed Original ResearchConceptsMetabotropic glutamate 2 receptorPrenatal stressSevere adverse life eventsSchizophrenia-like alterationsMaternal immune systemHead-twitch responsePrenatal immune activationAntipsychotic-like effectsAntipsychotic drug developmentMGlu2/3 agonist LY379268Risk of schizophreniaAdverse life eventsCross-fostering studyEarly neurodevelopmental originHallucinogenic 5Serotonin 2AAgonist DOIImmune activationAgonist LY379268Pathophysiological hypothesesFrontal cortexPsychiatric disordersAdult offspringSerotonin 5Behavioral alterationsHDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity
Kurita M, Holloway T, García-Bea A, Kozlenkov A, Friedman AK, Moreno JL, Heshmati M, Golden SA, Kennedy PJ, Takahashi N, Dietz DM, Mocci G, Gabilondo AM, Hanks J, Umali A, Callado LF, Gallitano AL, Neve RL, Shen L, Buxbaum JD, Han MH, Nestler EJ, Meana JJ, Russo SJ, González-Maeso J. HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity. Nature Neuroscience 2012, 15: 1245-1254. PMID: 22864611, PMCID: PMC3431440, DOI: 10.1038/nn.3181.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnimalsAntipsychotic AgentsBenzamidesChromatin ImmunoprecipitationClozapineDNA MethylationGenetic VectorsHEK293 CellsHerpesvirus 2, HumanHistone Deacetylase 2HistonesHumansHydroxamic AcidsImmunohistochemistryMiceMice, KnockoutPatch-Clamp TechniquesPlasmidsPrefrontal CortexPromoter Regions, GeneticPyridinesReal-Time Polymerase Chain ReactionReceptor, Serotonin, 5-HT2AReceptors, Metabotropic GlutamateReflex, StartleSchizophrenic PsychologyVorinostat
2018
HDAC2-dependent Antipsychotic-like Effects of Chronic Treatment with the HDAC Inhibitor SAHA in Mice
de la Fuente Revenga M, Ibi D, Saunders J, Cuddy T, Ijaz M, Toneatti R, Kurita M, Holloway T, Shen L, Seto J, Dozmorov M, González-Maeso J. HDAC2-dependent Antipsychotic-like Effects of Chronic Treatment with the HDAC Inhibitor SAHA in Mice. Neuroscience 2018, 388: 102-117. PMID: 30025863, PMCID: PMC6129430, DOI: 10.1016/j.neuroscience.2018.07.010.Peer-Reviewed Original ResearchConceptsHDAC inhibitor SAHAChronic treatmentControl miceFrontal cortexSchizophrenia patientsSynaptic plasticityChronic antipsychotic drug exposureHistone deacetylase 2 (HDAC2) expressionGlutamatergic pyramidal neuronsChronic antipsychotic treatmentAntipsychotic drug exposureAntipsychotic drug actionNew therapeutic approachesConditional knockout micePlasticity-related genesAntipsychotic treatmentPyramidal neuronsDrug exposureAntipsychotic drugsFunctional synapsesHDAC2 functionTherapeutic approachesKnockout micePresynaptic terminalsSAHA treatment
2016
HSV-Mediated Transgene Expression of Chimeric Constructs to Study Behavioral Function of GPCR Heteromers in Mice.
Holloway T, Moreno JL, González-Maeso J. HSV-Mediated Transgene Expression of Chimeric Constructs to Study Behavioral Function of GPCR Heteromers in Mice. Journal Of Visualized Experiments 2016 PMID: 27501227, PMCID: PMC4993366, DOI: 10.3791/53717.Peer-Reviewed Original ResearchConceptsHead-twitch responseLysergic acid diethylamideBehavioral effectsHead-twitch behaviorSchizophrenia-related behaviorsCortical pyramidal neuronsPowerful translational toolReceptor complexBehavioral phenotypesPyramidal neuronsFrontal cortexReceptor-dependent signaling pathwaysMouse modelHallucinogen DOIHeteromeric receptor complexesTranslational toolBehavioral responsesVirus constructsAcid diethylamideGPCR heteromersBehavioral functionsMiceHallucinogenic drugsSignaling pathwaysCortex
2013
Chronic treatment with LY341495 decreases 5-HT2A receptor binding and hallucinogenic effects of LSD in mice
Moreno JL, Holloway T, Rayannavar V, Sealfon SC, González-Maeso J. Chronic treatment with LY341495 decreases 5-HT2A receptor binding and hallucinogenic effects of LSD in mice. Neuroscience Letters 2013, 536: 69-73. PMID: 23333599, PMCID: PMC3578056, DOI: 10.1016/j.neulet.2012.12.053.Peer-Reviewed Original ResearchMeSH KeywordsAmino AcidsAnimalsDrug AntagonismEarly Growth Response Protein 1Early Growth Response Protein 2HallucinogensLysergic Acid DiethylamideMaleMiceMice, KnockoutProto-Oncogene Proteins c-fosRadioligand AssayReceptor, Serotonin, 5-HT2AReceptors, Metabotropic GlutamateSomatosensory CortexStereotyped BehaviorXanthenesConceptsLysergic acid diethylamideChronic treatmentHallucinogenic drugsHallucinogenic effectsHead-twitch behaviorHallucinogenic 5MGlu2 receptorLast injectionSomatosensory cortexLY341495Serotonin 5Receptor bindingAcid diethylamideC-fosReceptor ligandsMiceDrugsTreatmentEgr-2Egr-1ReceptorsBehavioral responsesKnockoutHigh affinityMetabotropicHDAC2 as a new target to improve schizophrenia treatment
Kurita M, Holloway T, González-Maeso J. HDAC2 as a new target to improve schizophrenia treatment. Expert Review Of Neurotherapeutics 2013, 13: 1-3. PMID: 23253383, PMCID: PMC3552246, DOI: 10.1586/ern.12.141.Peer-Reviewed Original Research
2012
Identification of Three Residues Essential for 5-Hydroxytryptamine 2A-Metabotropic Glutamate 2 (5-HT2A·mGlu2) Receptor Heteromerization and Its Psychoactive Behavioral Function*
Moreno JL, Muguruza C, Umali A, Mortillo S, Holloway T, Pilar-Cuéllar F, Mocci G, Seto J, Callado LF, Neve RL, Milligan G, Sealfon SC, López-Giménez JF, Meana JJ, Benson DL, González-Maeso J. Identification of Three Residues Essential for 5-Hydroxytryptamine 2A-Metabotropic Glutamate 2 (5-HT2A·mGlu2) Receptor Heteromerization and Its Psychoactive Behavioral Function*. Journal Of Biological Chemistry 2012, 287: 44301-44319. PMID: 23129762, PMCID: PMC3531745, DOI: 10.1074/jbc.m112.413161.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmino Acid MotifsAmino Acid SequenceAmino Acid SubstitutionAnimalsBehaviorCase-Control StudiesDimerizationFemaleHumansMaleMiceMice, 129 StrainMice, KnockoutMiddle AgedMolecular Sequence DataProtein BindingReceptor, Serotonin, 5-HT2AReceptors, Metabotropic GlutamateSchizophreniaSchizophrenic PsychologySequence AlignmentYoung AdultConceptsFrontal cortexMetabotropic glutamate 2 receptorGPCR heteromersBehavioral functionsMouse frontal cortexPsychosis-like effectsHallucinogenic 5Receptor neurotransmissionSchizophrenic subjectsReceptor heteromerizationReceptor complex formationSerotoninCortexHeteromeric expressionReceptorsReceptor heterocomplexDomain fourHeteromeric complexesCell signalingThree residuesHeteromersIntracellular endNeurotransmissionAgonistsMicePersistent effects of chronic clozapine on the cellular and behavioral responses to LSD in mice
Moreno JL, Holloway T, Umali A, Rayannavar V, Sealfon SC, González-Maeso J. Persistent effects of chronic clozapine on the cellular and behavioral responses to LSD in mice. Psychopharmacology 2012, 225: 217-226. PMID: 22842765, PMCID: PMC3552490, DOI: 10.1007/s00213-012-2809-7.Peer-Reviewed Original ResearchConceptsChronic clozapineLysergic acid diethylamideAtypical antipsychotic drug actionHead-twitch behaviorC-fosAntipsychotic-like activityAntipsychotic drug actionTherapeutic-like effectsMouse somatosensory cortexSchizophrenia-like behavioral alterationsEgr-2Egr-1Chronic haloperidolChronic treatmentClozapine administrationDrug therapyOptimal treatmentSomatosensory cortexSingle administrationAntipsychotic drugsMurine modelMouse modelRodent modelsSerotonin 5Behavioral alterations
2011
Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors
Albizu L, Holloway T, González-Maeso J, Sealfon SC. Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors. Neuropharmacology 2011, 61: 770-777. PMID: 21645528, PMCID: PMC3556730, DOI: 10.1016/j.neuropharm.2011.05.023.Peer-Reviewed Original ResearchConceptsMK-801-induced locomotor activityAlteration of serotoninDopamine D2 receptorsG protein-coupled receptor targetsFunctional crosstalkHEK293 cellsAntipsychotic effectsAntipsychotic drugsD2 receptorsSerotonin 5Dopamine systemLocomotor activityRadioligand bindingAgonist affinityReceptor targetsTherapeutic drugsReceptorsProduction assaysCo-immunoprecipitation studiesSerotoninReceptor heterocomplexDrugsActivationCellsAntagonistMaternal Influenza Viral Infection Causes Schizophrenia-Like Alterations of 5-HT2A and mGlu2 Receptors in the Adult Offspring
Moreno JL, Kurita M, Holloway T, López J, Cadagan R, Martínez-Sobrido L, García-Sastre A, González-Maeso J. Maternal Influenza Viral Infection Causes Schizophrenia-Like Alterations of 5-HT2A and mGlu2 Receptors in the Adult Offspring. Journal Of Neuroscience 2011, 31: 1863-1872. PMID: 21289196, PMCID: PMC3037097, DOI: 10.1523/jneurosci.4230-10.2011.Peer-Reviewed Original ResearchMeSH KeywordsAdult ChildrenAnimalsAntipsychotic AgentsCerebral CortexDisease Models, AnimalDown-RegulationEarly Growth Response Protein 1Early Growth Response Protein 2FemaleFrontal LobeGlutamic AcidHallucinogensInfluenza A Virus, H1N1 SubtypeMaternal-Fetal ExchangeMiceNeural PathwaysOrthomyxoviridae InfectionsPregnancyProto-Oncogene Proteins c-fosReceptor, Serotonin, 5-HT2AReceptors, Metabotropic GlutamateSchizophreniaUp-RegulationConceptsInfluenza viral infectionViral infectionMouse modelAdult offspringSchizophrenia-like alterationsPrenatal viral infectionHead-twitch responseSchizophrenia-like psychosisInfluenza A/WSN/33 virusMetabotropic glutamate receptorsAntipsychotic-like effectsPrevention of schizophreniaSpontaneous locomotor activityHigher c-fosEffects of hallucinogensBehavioral changesEgr-2 expressionEtiology of schizophreniaMechanism of actionMaternal infectionInfected mothersMaternal exposureGlutamate agonistsAntipsychotic drugsGlutamate systemMetabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists
Moreno JL, Holloway T, Albizu L, Sealfon SC, González-Maeso J. Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists. Neuroscience Letters 2011, 493: 76-79. PMID: 21276828, PMCID: PMC3064746, DOI: 10.1016/j.neulet.2011.01.046.Peer-Reviewed Original ResearchConceptsLysergic acid diethylamideHallucinogen DOIBehavioral effectsHead-twitch behaviorC-fosEgr-2Hallucinogenic 5MGlu2 receptorReceptor agonistKnockout miceHigh-affinity binding sitesNeuropsychological responsesMiceAgonistsAcid diethylamideHallucinogenic drugsSignaling pathwaysCellular signaling pathwaysReceptorsFunctional interactionMembrane preparationsBehavioral responsesResponseWild typeSerotonin