2021
Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior
Yasumoto Y, Stoiljkovic M, Kim JD, Sestan-Pesa M, Gao XB, Diano S, Horvath TL. Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior. Molecular Psychiatry 2021, 26: 2740-2752. PMID: 33879866, PMCID: PMC8056795, DOI: 10.1038/s41380-021-01105-1.Peer-Reviewed Original ResearchConceptsAnxiety-like behaviorReactive oxygen speciesMicroglia-synapse contactsSpine synapse numberHippocampal circuit functionNeuronal circuit dysfunctionMicroglial productionVentral hippocampusCircuit dysfunctionSpine synapsesSynapse numberAdult brainTransient riseMitochondrial ROS generationMicrogliaBrain functionConditional ablationPhagocytic inclusionsSynaptic elementsProtein 2ROS generationSignificant reductionCircuit functionConsequent accumulationOxygen species
2016
Role of mitochondrial uncoupling protein-2 (UCP2) in higher brain functions, neuronal plasticity and network oscillation
Hermes G, Nagy D, Waterson M, Zsarnovszky A, Varela L, Hajos M, Horvath TL. Role of mitochondrial uncoupling protein-2 (UCP2) in higher brain functions, neuronal plasticity and network oscillation. Molecular Metabolism 2016, 5: 415-421. PMID: 27257601, PMCID: PMC4877662, DOI: 10.1016/j.molmet.2016.04.002.Peer-Reviewed Original ResearchMouse modelSynaptic plasticityMental illnessUCP2 knockout miceNMDA receptor blockadeHigher brain regionsKO mouse modelMajor psychiatric illnessProtein 2 expressionHigher brain functionsReceptor blockadePsychiatric illnessNeuronal plasticityKnockout miceNeural transmissionCellular resilienceCortical activityBrain regionsProfound disorderBrain functionMitochondrial impairmentIllnessNetwork oscillationsMitochondrial functionProtein 2Mitochondrial Uncoupling Protein 2 (UCP2) Regulates Retinal Ganglion Cell Number and Survival
Barnstable CJ, Reddy R, Li H, Horvath TL. Mitochondrial Uncoupling Protein 2 (UCP2) Regulates Retinal Ganglion Cell Number and Survival. Journal Of Molecular Neuroscience 2016, 58: 461-469. PMID: 26846222, PMCID: PMC4833669, DOI: 10.1007/s12031-016-0728-5.Peer-Reviewed Original ResearchConceptsRetinal ganglion cellsUncoupling protein 2Mitochondrial uncoupling protein 2Ganglion cellsRetinal ganglion cell numberNeurotrophic factor BDNFSurvival-promoting effectsGanglion cell numberUCP2 levelsRetinal neuron survivalProtein 2Critical developmental periodIntraocular injectionKainic acidNeuron survivalNeuronal survivalMouse retinaRetinal cellsElevated numbersAdult animalsSurvivalCell numberCell survivalImportant regulatorCell death
2013
Antibodies to cannabinoid type 1 receptor co‐react with stomatin‐like protein 2 in mouse brain mitochondria
Morozov YM, Dominguez MH, Varela L, Shanabrough M, Koch M, Horvath TL, Rakic P. Antibodies to cannabinoid type 1 receptor co‐react with stomatin‐like protein 2 in mouse brain mitochondria. European Journal Of Neuroscience 2013, 38: 2341-2348. PMID: 23617247, PMCID: PMC3902808, DOI: 10.1111/ejn.12237.Peer-Reviewed Original ResearchConceptsStomatin-like protein 2Type 1 receptorPresence of CB1Protein 2Anti-CB1 antibodySynthetic cannabinoid WINMouse brain mitochondriaCerebral cortexEndocannabinoid signalingBrain cellsCannabinoid WINNeuronal mitochondriaBrain mitochondriaAntibodiesMitochondrial functionCB1Polyclonal antibodiesCortexMitochondrial preparationsSerumReceptors
2012
Ucp2 Induced by Natural Birth Regulates Neuronal Differentiation of the Hippocampus and Related Adult Behavior
Simon-Areces J, Dietrich MO, Hermes G, Garcia-Segura LM, Arevalo MA, Horvath TL. Ucp2 Induced by Natural Birth Regulates Neuronal Differentiation of the Hippocampus and Related Adult Behavior. PLOS ONE 2012, 7: e42911. PMID: 22905184, PMCID: PMC3414493, DOI: 10.1371/journal.pone.0042911.Peer-Reviewed Original ResearchConceptsUCP2 expressionCellular stressHippocampal neuronsChemical inhibitionMitochondrial bioenergeticsNeuronal differentiationGenetic ablationNatural birthProtein 2Adult behaviorCell proliferationCritical roleAdult brainNeuronal numberExpressionBioenergeticsNeuronsBirthDifferentiationRegulationProliferationSynaptogenesisVitroNeuroprotectionHippocampus
2011
Mitochondrial uncoupling protein 2 (UCP2) in glucose and lipid metabolism
Diano S, Horvath TL. Mitochondrial uncoupling protein 2 (UCP2) in glucose and lipid metabolism. Trends In Molecular Medicine 2011, 18: 52-58. PMID: 21917523, DOI: 10.1016/j.molmed.2011.08.003.Peer-Reviewed Original ResearchConceptsProtein 2Lipid metabolismExcess of nutrientsHypothalamic neuronal circuitsNutrient availabilityPeripheral tissue functionsPhysiological functionsMetabolism regulationChronic diseasesMetabolism-related chronic diseasesTissue functionFuture therapeutic strategiesPathological processesPeripheral mechanismsLipid levelsNeuronal circuitsTherapeutic strategiesMetabolismImpairs healthMitochondriaDiseaseUCP2GlucoseRegulationNutrients
2010
Uncoupling Protein-2 Decreases the Lipogenic Actions of Ghrelin
Andrews ZB, Erion DM, Beiler R, Choi CS, Shulman GI, Horvath TL. Uncoupling Protein-2 Decreases the Lipogenic Actions of Ghrelin. Endocrinology 2010, 151: 2078-2086. PMID: 20189996, PMCID: PMC2869261, DOI: 10.1210/en.2009-0850.Peer-Reviewed Original ResearchConceptsBody weight gainGhrelin treatmentWeight gainLipogenic actionsBody weightFat oxidationFat metabolismChronic ghrelin treatmentDaily ip injectionsWhite adipose tissueNegative energy balanceCalorie restriction modelOsmotic minipumpsIP injectionBody fatGhrelinAdipose tissueMiceReactive oxygen speciesExact mechanismUCP2 mRNALipogenesisProtein 2Oxygen speciesTreatment
2009
Uncoupling protein-2 regulates lifespan in mice
Andrews ZB, Horvath TL. Uncoupling protein-2 regulates lifespan in mice. AJP Endocrinology And Metabolism 2009, 296: e621-e627. PMID: 19141680, PMCID: PMC2670629, DOI: 10.1152/ajpendo.90903.2008.Peer-Reviewed Original ResearchConceptsDifferent tissuesProtein 2Uncoupled mitochondrial respirationReactive oxygen species productionMammalian physiologyMutant animalsOxygen species productionMitochondrial respirationLevels of UCP2Species productionTissue functionLong lifespanUCP2Oxidative stressLifespanPostnatal survivalWild-type miceMiceTissuePhysiologyRespirationCells
2008
UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals
Andrews ZB, Liu ZW, Walllingford N, Erion DM, Borok E, Friedman JM, Tschöp MH, Shanabrough M, Cline G, Shulman GI, Coppola A, Gao XB, Horvath TL, Diano S. UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals. Nature 2008, 454: 846-851. PMID: 18668043, PMCID: PMC4101536, DOI: 10.1038/nature07181.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsCarnitine O-PalmitoyltransferaseFatty AcidsFeeding BehaviorGene Expression RegulationGhrelinHypothalamusIon ChannelsMembrane Potential, MitochondrialMiceMitochondriaMitochondrial ProteinsNeuronsNeuropeptide YPhosphorylationReactive Oxygen SpeciesSynapsesUncoupling Protein 2ConceptsNPY/AgRP neuronsAgRP neuronsNeuronal activityCo-express neuropeptide YGut-derived hormone ghrelinAgRP neuronal activityArcuate nucleus neuronsFatty acid oxidation pathwayHypothalamic mitochondrial respirationG protein-coupled receptorsGhrelin actionNeuropeptide YNucleus neuronsHormone ghrelinFood intakeGhrelinFree radicalsSynaptic plasticityNeuronal functionIntracellular mechanismsNeuronsMitochondrial mechanismsProtein 2Mitochondrial proliferationRobust changes
2007
A Central Thermogenic-like Mechanism in Feeding Regulation: An Interplay between Arcuate Nucleus T3 and UCP2
Coppola A, Liu ZW, Andrews ZB, Paradis E, Roy MC, Friedman JM, Ricquier D, Richard D, Horvath TL, Gao XB, Diano S. A Central Thermogenic-like Mechanism in Feeding Regulation: An Interplay between Arcuate Nucleus T3 and UCP2. Cell Metabolism 2007, 5: 21-33. PMID: 17189204, PMCID: PMC1783766, DOI: 10.1016/j.cmet.2006.12.002.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsArcuate Nucleus of HypothalamusEatingFastingFeeding BehaviorGreen Fluorescent ProteinsGuanosine DiphosphateHypothalamusIntercellular Signaling Peptides and ProteinsIodide PeroxidaseIon ChannelsMiceMice, Inbred C57BLMice, KnockoutMitochondriaMitochondrial ProteinsNeurogliaNeuronsNeuropeptide YProto-Oncogene Proteins c-fosThermogenesisTriiodothyronineUncoupling Protein 2ConceptsUncoupling protein 2Mitochondrial uncoupling protein 2Thyroid hormone productionProtein activityType 2 deiodinaseMitochondrial proliferationNeuropeptide YArcuate nucleusPhysiological roleMitochondrial uncouplingUCP2 activationProtein 2Hormone productionNPY/AgRP neuronsPhysiological significanceActive thyroid hormoneHypothalamic arcuate nucleusHypothalamic neuronal networksGlial cellsRebound feedingAgRP neuronsOrexigenic neuronsDeiodinaseDII activityPeripheral tissues
2006
Uncoupling protein‐2 promotes nigrostriatal dopamine neuronal function
Andrews ZB, Rivera A, Elsworth JD, Roth RH, Agnati L, Gago B, Abizaid A, Schwartz M, Fuxe K, Horvath TL. Uncoupling protein‐2 promotes nigrostriatal dopamine neuronal function. European Journal Of Neuroscience 2006, 24: 32-36. PMID: 16882005, DOI: 10.1111/j.1460-9568.2006.04906.x.Peer-Reviewed Original ResearchMeSH Keywords3,4-Dihydroxyphenylacetic AcidAnimalsCorpus StriatumDopamineDopamine Plasma Membrane Transport ProteinsImmunohistochemistryIon ChannelsMaleMembrane Transport ProteinsMiceMice, KnockoutMitochondrial ProteinsMotor ActivityNeuronsSubstantia NigraTyrosine 3-MonooxygenaseUncoupling Protein 2ConceptsSubstantia nigra pars compactaDopamine neuronal functionUCP2-KO miceParkinson's diseaseNeuronal functionNigrostriatal dopamine functionTyrosine hydroxylase immunoreactivityUCP2 knockout miceDopamine transporter immunoreactivityProtein 2Wild-type controlsHydroxylase immunoreactivityPars compactaDopamine turnoverTransporter immunoreactivityDopamine ratioBehavioral deficitsLocomotor functionNucleus accumbensBiochemical deficitsDopamine functionBrain regionsNeurological pathologiesDiseaseMice
2005
Uncoupling protein 2 protects dopaminergic neurons from acute 1,2,3,6‐methyl‐phenyl‐tetrahydropyridine toxicity
Conti B, Sugama S, Lucero J, Winsky‐Sommerer R, Wirz SA, Maher P, Andrews Z, Barr AM, Morale MC, Paneda C, Pemberton J, Gaidarova S, Behrens MM, Beal F, Sanna PP, Horvath T, Bartfai T. Uncoupling protein 2 protects dopaminergic neurons from acute 1,2,3,6‐methyl‐phenyl‐tetrahydropyridine toxicity. Journal Of Neurochemistry 2005, 93: 493-501. PMID: 15816872, DOI: 10.1111/j.1471-4159.2005.03052.x.Peer-Reviewed Original ResearchConceptsDopaminergic neuronsParkinson's diseaseOxidative stressSpecific neuronal expressionTyrosine hydroxylase promoterTetrahydropyridine (MPTP) toxicityCatecholaminergic neuronsSubstantia nigraHydroxylase promoterLocomotor functionMouse modelNeuronal expressionAcute exposureTransgenic miceSporadic formsTwofold elevationUCP2 expressionDiseaseMarked reductionNeuronsMiceNeuroprotectionProtein 2UCP familyDrug targetsUncoupling Protein-2 Is Critical for Nigral Dopamine Cell Survival in a Mouse Model of Parkinson's Disease
Andrews ZB, Horvath B, Barnstable CJ, Elseworth J, Yang L, Beal MF, Roth RH, Matthews RT, Horvath TL. Uncoupling Protein-2 Is Critical for Nigral Dopamine Cell Survival in a Mouse Model of Parkinson's Disease. Journal Of Neuroscience 2005, 25: 184-191. PMID: 15634780, PMCID: PMC6725213, DOI: 10.1523/jneurosci.4269-04.2005.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine1-Methyl-4-phenylpyridiniumAnimalsCell SurvivalCorpus StriatumDisease Models, AnimalDopamineHumansImmunohistochemistryIon ChannelsMaleMembrane Transport ProteinsMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMitochondriaMitochondrial ProteinsOxygen ConsumptionParkinsonian DisordersReactive Oxygen SpeciesSubstantia NigraUncoupling Protein 2ConceptsProtein 2Mitochondrial ROS productionLack of UCP2Reactive oxygen species productionGenetic manipulationOxygen species productionMitochondria numberCell metabolismATP synthesisCell survivalOverexpression of UCP2Wild-type controlsMitochondrial uncouplingNovel therapeutic targetROS productionUCP2Species productionElectron microscopic analysisOverexpressionCell functionUCP2 overexpressionDopamine cell survivalTherapeutic targetFluorescent ethidiumDopamine cell function
2004
Dynamics of volume transmission in the brain. Focus on catecholamine and opioid peptide communication and the role of uncoupling protein 2
Fuxe K, Rivera A, Jacobsen KX, Höistad M, Leo G, Horvath TL, Staines W, De la Calle A, Agnati LF. Dynamics of volume transmission in the brain. Focus on catecholamine and opioid peptide communication and the role of uncoupling protein 2. Journal Of Neural Transmission 2004, 112: 65-76. PMID: 15599605, DOI: 10.1007/s00702-004-0158-3.Peer-Reviewed Original Research
2003
Uncoupling Protein 2 Prevents Neuronal Death Including that Occurring during Seizures: A Mechanism for Preconditioning
Diano S, Matthews RT, Patrylo P, Yang L, Beal MF, Barnstable CJ, Horvath TL. Uncoupling Protein 2 Prevents Neuronal Death Including that Occurring during Seizures: A Mechanism for Preconditioning. Endocrinology 2003, 144: 5014-5021. PMID: 12960023, DOI: 10.1210/en.2003-0667.Peer-Reviewed Original ResearchConceptsFree radical-induced cell deathFree radical-induced damageCell deathSeizure inductionSeizure activityNeuronal deathRadical-induced damageTransgenic miceNeurodegenerative disordersCellular stressRobust reductionUCP2 levelsParallel decreaseDeathATP levelsPC12 cellsProtein 2Mitochondrial uncoupling proteinUCP2Mitochondrial numberCellular energy productionFree radicalsHarmful effectsUncoupling proteinEpilepsyMitochondrial 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 understandingUncoupler
2002
Uncoupling protein 2 in primary pain and temperature afferents of the spinal cord
Horvath B, Spies C, Warden CH, Diano S, Horvath TL. Uncoupling protein 2 in primary pain and temperature afferents of the spinal cord. Brain Research 2002, 955: 260-263. PMID: 12419545, DOI: 10.1016/s0006-8993(02)03364-4.Peer-Reviewed Original ResearchConceptsSpinal cordExpression of UCP2Primary sensory afferentsMechanisms of painProtein 2Primary painSensory afferentsSubstantia gelatinosaVentral hornSubstance P.Axon terminalsCordEnergy homeostasisUCP2 expressionDirect appositionTemperature sensationMitochondrial protonophorePainAfferentsUCP2Mitochondrial uncouplerCellular energy homeostasisExpressionPerikaryaAxonsBrain mitochondrial uncoupling protein 2 (UCP2): a protective stress signal in neuronal injury
Bechmann I, Diano S, Warden CH, Bartfai T, Nitsch R, Horvath TL. Brain mitochondrial uncoupling protein 2 (UCP2): a protective stress signal in neuronal injury. Biochemical Pharmacology 2002, 64: 363-367. PMID: 12147286, DOI: 10.1016/s0006-2952(02)01166-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedBrain InjuriesDisease Models, AnimalEntorhinal CortexGene Transfer TechniquesImmunohistochemistryIon ChannelsLearningMaleMembrane Transport ProteinsMemoryMiceMice, Inbred C57BLMitochondriaMitochondrial ProteinsNerve DegenerationNeuronsProtective AgentsProteinsRatsRats, WistarSignal TransductionStress, PhysiologicalUncoupling Protein 2Uncoupling 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