2025
Reduced DJ-1-F1Fo ATP synthase association correlates with midbrain dopaminergic neuron vulnerability in idiopathic Parkinson’s disease
Abulimiti A, Bae H, Ali A, Balakrishnan S, Tsujishita M, Gveric D, Tierney T, Jonas E, Smith P, Gentleman S, Alavian K. Reduced DJ-1-F1Fo ATP synthase association correlates with midbrain dopaminergic neuron vulnerability in idiopathic Parkinson’s disease. Science Advances 2025, 11: eads3051. PMID: 40479058, PMCID: PMC12143374, DOI: 10.1126/sciadv.ads3051.Peer-Reviewed Original ResearchConceptsProximity ligation assayVentral tegmental areaF1Fo-ATP synthaseProximity ligation assay signalsMetabolic efficiencyVentral tegmental area neuronsMitochondrial metabolic efficiencyProtein productionLigation assayMitochondrial activityMetabolic homeostasisIntracellular compartmentsMitochondrial efficiencyDistal neuritesParkinson's diseaseControl postmortem brainsImpaired mitochondrial efficiencySubstantia nigra pars compactaDopaminergic neuron vulnerabilityMesDA neuronsMesencephalic dopaminergicNeuronal vulnerabilityTegmental areaNeuronal subpopulationsIdiopathic Parkinson's diseaseBeyond hedonic eating
Small D. Beyond hedonic eating. Science 2025, 387: 1353-1354. PMID: 40146849, DOI: 10.1126/science.adw3646.Peer-Reviewed Original ResearchCCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson’s disease models
Leser F, Júnyor F, Pagnoncelli I, Delgado A, Medeiros I, Nóbrega A, Andrade B, de Lima M, da Silva N, Jacob L, Boyé K, Geraldo L, de Souza A, Maron-Gutierrez T, Castro-Faria-Neto H, Follmer C, Braga C, Neves G, Eichmann A, Romão L, Lima F. CCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson’s disease models. Journal Of Neuroinflammation 2025, 22: 31. PMID: 39894839, PMCID: PMC11789347, DOI: 10.1186/s12974-024-03318-x.Peer-Reviewed Original ResearchConceptsMouse model of PDModel of PDMouse modelDopaminergic neuronsNeuron-microglia communicationNeuron-glia communicationParkinson's diseaseCCR7-dependent mannerMicroglial cell activationCCR7 expressionCCL21-CCR7Progressive degenerative diseaseCCR7 receptorMicroglial cell migrationInflammatory profileChemokine CCL21Cell activationCCL21Therapeutic strategiesChemokine inhibitorsTherapeutic implicationsMicroglial activationReceptor pathwayCCR7Behavioral deficitsContextual cues facilitate dynamic value encoding in the mesolimbic dopamine system
Fraser K, Collins V, Wolff A, Ottenheimer D, Bornhoft K, Pat F, Chen B, Janak P, Saunders B. Contextual cues facilitate dynamic value encoding in the mesolimbic dopamine system. Current Biology 2025, 35: 746-760.e5. PMID: 39855205, PMCID: PMC11859769, DOI: 10.1016/j.cub.2024.12.031.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsConditioning, ClassicalCuesDopamineDopaminergic NeuronsFemaleMaleMotivationNucleus AccumbensRatsRats, Long-EvansRewardVentral Tegmental AreaConceptsMesolimbic dopamine systemConditioned stimulusDopamine systemNucleus accumbensDopamine functionDopamine releaseOccasion setterDopamine neuronsActivity of ventral tegmental area dopamine neuronsVentral tegmental area dopamine neuronsTheory of dopamine functionNon-overlapping presentationSucrose deliverySucrose rewardContextual cuesBehavioral outputAdaptive behaviorDynamic environmental contextBehavioral responsesFemale ratsAccumbensStimuliSeeking behaviorDopamineMotor control
2024
Parkinsonism Sac domain mutation in Synaptojanin-1 affects ciliary properties in iPSC-derived dopaminergic neurons
Rafiq N, Fujise K, Rosenfeld M, Xu P, De Camilli P. Parkinsonism Sac domain mutation in Synaptojanin-1 affects ciliary properties in iPSC-derived dopaminergic neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2318943121. PMID: 38635628, PMCID: PMC11047088, DOI: 10.1073/pnas.2318943121.Peer-Reviewed Original ResearchConceptsSynaptojanin 1Endocytic factorsDA neuronsCilia-mediated signalingNerve terminalsIPSC-derived dopaminergic neuronsUbiquitin chainsUbiquitinated proteinsCiliary baseCilia lengthNeurological defectsDopaminergic neuronsProtein dynamicsDomain mutationsAssembly stateIsogenic controlsNeuronsAbnormal accumulationMutationsMiceFocal concentrationParkinsonPI(4UbiquitinEndocytosis
2022
AgRP neurons control structure and function of the medial prefrontal cortex
Stutz B, Waterson MJ, Šestan-Peša M, Dietrich MO, Škarica M, Sestan N, Racz B, Magyar A, Sotonyi P, Liu ZW, Gao XB, Matyas F, Stoiljkovic M, Horvath TL. AgRP neurons control structure and function of the medial prefrontal cortex. Molecular Psychiatry 2022, 27: 3951-3960. PMID: 35906488, PMCID: PMC9891653, DOI: 10.1038/s41380-022-01691-8.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsDopaminergic NeuronsHypothalamusMiceNeuropeptide YPrefrontal CortexConceptsMedial prefrontal cortexAgRP neuronsNon-selective dopamine receptor antagonistBrain functionPrefrontal cortexHypothalamic AgRP neuronsMedial thalamic neuronsAdministration of clozapineDopamine receptor antagonistVentral tegmental areaOscillatory network activityHigher-order brain functionsHypothalamic agoutiThalamic neuronsChemogenetic inhibitionDopaminergic neuronsReceptor antagonistTegmental areaNeuronal pathwaysSensorimotor gatingAdult miceModulatory impactAmbulatory behaviorConstitutive impairmentNeuronsThe immunology of Parkinson’s disease
Zhu B, Yin D, Zhao H, Zhang L. The immunology of Parkinson’s disease. Seminars In Immunopathology 2022, 44: 659-672. PMID: 35674826, PMCID: PMC9519672, DOI: 10.1007/s00281-022-00947-3.Peer-Reviewed Original ResearchMeSH Keywordsalpha-SynucleinBrainDopaminergic NeuronsHumansNeurodegenerative DiseasesParkinson DiseaseConceptsAdaptive immune responsesImmune responseParkinson's diseaseT cellsGut-brain axis hypothesisOnset of PDΑ-synucleinGastro-intestinal symptomsCommon neurodegenerative disorderInnate immune responseΑ-synuclein aggregationPD patientsDopaminergic neuronsLewy bodiesSubstantia nigraNeuronal deathDisease progressionNeuropathological hallmarksProdromal phaseCurrent treatmentNeurodegenerative disordersDiseaseBrainMicrogliaPatients
2021
Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease risk
Powell SK, O’Shea C, Townsley K, Prytkova I, Dobrindt K, Elahi R, Iskhakova M, Lambert T, Valada A, Liao W, Ho SM, Slesinger PA, Huckins LM, Akbarian S, Brennand KJ. Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease risk. Molecular Psychiatry 2021, 28: 1970-1982. PMID: 34493831, PMCID: PMC8898985, DOI: 10.1038/s41380-021-01273-0.Peer-Reviewed Original ResearchMeSH KeywordsAutism Spectrum DisorderDopaminergic NeuronsHumansInduced Pluripotent Stem CellsMesencephalonReproducibility of ResultsConceptsInduced dopaminergic neuronsDopaminergic neuronsMidbrain dopaminergic neuron developmentNeuron identityHuman induced pluripotent stem cellsCannabis use disorderDopaminergic neuron developmentAction potential durationGlutamatergic neuronsDopamine synthesisSpontaneous burstsPotential durationUse disordersNeuronal subtypesPsychiatric diseasesBipolar disorderElectrophysiological propertiesDisease riskHyperpolarization potentialPsychiatric disease riskNeuron developmentOscillatory activityNeuronsHeterogenous cell populationsCell populationsDopaminergic mechanism underlying reward-encoding of punishment omission during reversal learning in Drosophila
McCurdy LY, Sareen P, Davoudian PA, Nitabach MN. Dopaminergic mechanism underlying reward-encoding of punishment omission during reversal learning in Drosophila. Nature Communications 2021, 12: 1115. PMID: 33602917, PMCID: PMC7893153, DOI: 10.1038/s41467-021-21388-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAvoidance LearningConditioning, ClassicalDopamineDopaminergic NeuronsDrosophila melanogasterMemoryPunishmentReversal LearningRewardSmellSynapsesConceptsDopaminergic neuronsCholinergic neuronsNeural circuit mechanismsCholinergic relayDopaminergic mechanismsSynaptic excitationSynaptic reconstructionSynaptic inputsVivo functional imagingCircuit mechanismsNeuronsAversive memoryFunctional imagingOdor responsesAversive outcomesReduced activationSuch activationCircuit motifsActivationOutcomesElectric shock punishmentSensory cuesUnexpected omissionShock punishmentBehavioral analysis
2020
Mitomycin-C treatment during differentiation of induced pluripotent stem cell-derived dopamine neurons reduces proliferation without compromising survival or function in vivo
Hiller B, Marmion D, Gross R, Thompson C, Chavez C, Brundin P, Wakeman D, McMahon C, Kordower J. Mitomycin-C treatment during differentiation of induced pluripotent stem cell-derived dopamine neurons reduces proliferation without compromising survival or function in vivo. Stem Cells Translational Medicine 2020, 10: 278-290. PMID: 32997443, PMCID: PMC7848297, DOI: 10.1002/sctm.20-0014.Peer-Reviewed Original ResearchConceptsDopamine neuronsInduced pluripotent stem cellsParkinson's diseaseStem cell-derived dopamine neuronsPD cell therapyMidbrain dopamine neuronsLong-term survivalTransplant of cellsStem cellsHuman induced pluripotent stem cellsPluripotent stem cellsNeuron preparationsMitomycin C treatmentAthymic ratsDrug selectionUndesirable proliferationCell therapyRobust survivalLower proliferationVivo functionNeuronsTransplantationSurvivalProliferative cellsDiseaseGeneration of Pluripotent Stem Cells Using Somatic Cell Nuclear Transfer and Induced Pluripotent Somatic Cells from African Green Monkeys
Chung YG, Seay M, Elsworth J, Redmond D. Generation of Pluripotent Stem Cells Using Somatic Cell Nuclear Transfer and Induced Pluripotent Somatic Cells from African Green Monkeys. Stem Cells And Development 2020, 29: 1294-1307. PMID: 32715987, DOI: 10.1089/scd.2020.0059.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCell LineChlorocebus aethiopsChromosome BandingCloning, OrganismCulture MediaCytogenetic AnalysisDNADopaminergic NeuronsEmbryonic DevelopmentEmbryonic Stem CellsFemaleGenotypeHumansInduced Pluripotent Stem CellsMitochondriaNuclear Transfer TechniquesOvaryTyrosine 3-MonooxygenaseConceptsAfrican green monkeysInduced pluripotent stem cellsCell linesGreen monkeysStem cellsEffective cell replacement therapyPromising potential therapyPluripotent stem cellsDopamine depletionReplacement therapyDopamine neuronsCell replacement therapyBrain pathologyDonor monkeyParkinson's diseasePotential therapyMonkey studiesFemale monkeysClinical predictive powerImmune rejectionImmune systemAccidental exposurePossible treatmentIPSC linesRodent experiments
2019
Deletion of the Creatine Transporter (Slc6a8) in Dopaminergic Neurons Leads to Hyperactivity in Mice
Abdulla ZI, Pahlevani B, Lundgren KH, Pennington JL, Udobi KC, Seroogy KB, Skelton MR. Deletion of the Creatine Transporter (Slc6a8) in Dopaminergic Neurons Leads to Hyperactivity in Mice. Journal Of Molecular Neuroscience 2019, 70: 102-111. PMID: 31520365, PMCID: PMC7001766, DOI: 10.1007/s12031-019-01405-w.Peer-Reviewed Original ResearchConceptsCr transporter deficiencyDopaminergic neuronsMotor functionLocomotor activityChallenging beam testSpontaneous activity testMonths of ageAttention deficit hyperactivity disorderCerebral Cr deficiencySpecific neuronal systemsUnique metabolic demandsCerebral creatineHindlimb stepsControl miceNeurological effectsSpontaneous activityMice ageSLC6A8 geneTransporter deficiencyNeurodegenerative disordersDopamine transporterNeuronal systemsMiceCreatine transporterHuntington's diseaseParkinson’s disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth
Chen R, Park HA, Mnatsakanyan N, Niu Y, Licznerski P, Wu J, Miranda P, Graham M, Tang J, Boon AJW, Cossu G, Mandemakers W, Bonifati V, Smith PJS, Alavian KN, Jonas EA. Parkinson’s disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth. Cell Death & Disease 2019, 10: 469. PMID: 31197129, PMCID: PMC6565618, DOI: 10.1038/s41419-019-1679-x.Peer-Reviewed Original ResearchConceptsDJ-1C subunitATP synthaseParkinson's disease protein DJ-1Β-subunitProtein componentsATP synthase β subunitMitochondrial uncouplingDJ-1 bindsATP synthase efficiencyATP synthase F1Synthase β subunitATP production efficiencyProtein DJ-1Neuronal process extensionProtein levelsNeuronal process outgrowthDJ-1 knockoutWild-type counterpartsSubunit protein levelsDJ-1 mutationsSevere defectsCell metabolismKO neuronsKO culturesEmbryonic and postnatal development of mouse olfactory tubercle
Martin-Lopez E, Xu C, Liberia T, Meller SJ, Greer CA. Embryonic and postnatal development of mouse olfactory tubercle. Molecular And Cellular Neuroscience 2019, 98: 82-96. PMID: 31200100, PMCID: PMC11993912, DOI: 10.1016/j.mcn.2019.06.002.Peer-Reviewed Original ResearchConceptsOlfactory tubercleVentral striatumOlfactory bulb projection neuronsPrimary afferent inputTyrosine hydroxylase expressionLateral ganglionic eminenceDopamine reward systemCNPase stainingVentral medial regionDopaminergic innervationProjection neuronsStriatal neuronsVentral tegmentumAfferent inputDopaminergic inputLaminar distributionMedial gradientHydroxylase expressionNucleus accumbensGanglionic eminencePostnatal developmentE11-E15OT cellsVentral lateral ganglionic eminencePostnatal stagesFTY720 Inhibits MPP+-Induced Microglial Activation by Affecting NLRP3 Inflammasome Activation
Yao S, Li L, Sun X, Hua J, Zhang K, Hao L, Liu L, Shi D, Zhou H. FTY720 Inhibits MPP+-Induced Microglial Activation by Affecting NLRP3 Inflammasome Activation. Journal Of Neuroimmune Pharmacology 2019, 14: 478-492. PMID: 31069623, DOI: 10.1007/s11481-019-09843-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntiparkinson AgentsApoptosisCell LineCorpus StriatumCytokinesDopaminergic NeuronsDrug Evaluation, PreclinicalExploratory BehaviorFingolimod HydrochlorideInflammasomesMaleMiceMice, Inbred C57BLMicrogliaMitochondriaMPTP PoisoningNeuroprotective AgentsNLR Family, Pyrin Domain-Containing 3 ProteinParkinsonian DisordersPars CompactaReactive Oxygen SpeciesRotarod Performance TestSignal TransductionConceptsTherapeutic effects of FTY720Effect of FTY720Therapeutic effectNLRP3 inflammasome activationDopaminergic neuronsMicroglial activationP65 activationInflammasome activationSubcutaneous injection of MPTPMPTP-induced microglial activationIncreased dopamine releaseMPTP-induced behavioral deficitsDamage to dopaminergic neuronsTumor necrosis factor-aAnimal models of PDInjection of MPTPROS generationSubstantia nigra pars compactaDecreased NLRP3 inflammasome activationParkinson's diseaseInterleukin (IL)-6Production of interleukin (IL)-6Degeneration of dopaminergic neuronsLoss of dopaminergic neuronsActivation of microgliaDopamine neuronal protection in the mouse Substantia nigra by GHSR is independent of electric activity
Stutz B, Nasrallah C, Nigro M, Curry D, Liu ZW, Gao XB, Elsworth JD, Mintz L, Horvath TL. Dopamine neuronal protection in the mouse Substantia nigra by GHSR is independent of electric activity. Molecular Metabolism 2019, 24: 120-138. PMID: 30833218, PMCID: PMC6531791, DOI: 10.1016/j.molmet.2019.02.005.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsDopaminergic NeuronsGhrelinMiceMPTP PoisoningNeuroprotective AgentsPeptide FragmentsReceptors, GhrelinSubstantia NigraConceptsSN DA neuronsDA neuronsSubstantia nigraDA cellsDopamine outputNeuronal protectionNeuronal survivalParkinson's diseaseDA neuron survivalDA neuronal survivalDesigner drugs (DREADD) technologyNeuronal pacemaker activityElectrical activityMouse substantia nigraElectric activityNeuron electrical activityAnimal motor behaviorGhrelin activationGHSR activationTetrahydropyridine (MPTP) treatmentNeuroprotective factorsNeuron survivalDopamine neuronsGhrelin receptorExogenous administration
2018
A Neural Circuit for Gut-Induced Reward
Han W, Tellez LA, Perkins MH, Perez IO, Qu T, Ferreira J, Ferreira TL, Quinn D, Liu ZW, Gao XB, Kaelberer MM, Bohórquez DV, Shammah-Lagnado SJ, de Lartigue G, de Araujo IE. A Neural Circuit for Gut-Induced Reward. Cell 2018, 175: 665-678.e23. PMID: 30245012, PMCID: PMC6195474, DOI: 10.1016/j.cell.2018.08.049.Peer-Reviewed Original ResearchMeSH KeywordsAfferent PathwaysAnimalsDopamineDopaminergic NeuronsGlutamic AcidIntestinesMaleMiceMice, Inbred C57BLOptogeneticsRewardSubstantia NigraVagus NerveConceptsSubstantia nigraVagal sensory gangliaVagal sensory neuronsTransneuronal labelingTransneuronal tracingVagal originBrain axisGlutamatergic neuronsSelf-stimulation behaviorParabrachial regionSensory gangliaDopamine cellsObligatory relayDopamine releaseSensory neuronsRewarding effectsNeuronal circuitryPlace preferenceReward pathwayNeural circuitsNeuronsStimulation approachesReward neuronsMajor regulatorNigraα1- and β3-Adrenergic Receptor–Mediated Mesolimbic Homeostatic Plasticity Confers Resilience to Social Stress in Susceptible Mice
Zhang H, Chaudhury D, Nectow AR, Friedman AK, Zhang S, Juarez B, Liu H, Pfau ML, Aleyasin H, Jiang C, Crumiller M, Calipari ES, Ku SM, Morel C, Tzavaras N, Montgomery SE, He M, Salton SR, Russo SJ, Nestler EJ, Friedman JM, Cao JL, Han MH. α1- and β3-Adrenergic Receptor–Mediated Mesolimbic Homeostatic Plasticity Confers Resilience to Social Stress in Susceptible Mice. Biological Psychiatry 2018, 85: 226-236. PMID: 30336931, PMCID: PMC6800029, DOI: 10.1016/j.biopsych.2018.08.020.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-1 Receptor AgonistsAdrenergic alpha-1 Receptor AntagonistsAdrenergic beta-3 Receptor AgonistsAdrenergic beta-3 Receptor AntagonistsAnimalsBehavior, AnimalDopaminergic NeuronsHomeostasisLocus CoeruleusMaleMiceNeural PathwaysNeuronal PlasticityReceptors, Adrenergic, alpha-1Receptors, Adrenergic, beta-3Resilience, PsychologicalStress, PsychologicalVentral Tegmental AreaConceptsSocial defeat stressDA neuronsSusceptible miceHomeostatic plasticityLocus coeruleusDefeat stressAdrenergic receptorsChronic social defeat stress (CSDS) modelSocial defeat stress modelVTA DA neuronsDepression-related behaviorsMesolimbic DA neuronsMesolimbic dopamine neuronsΒ3-adrenergic receptorMolecular profiling studiesNew molecular targetsSocial stressCircuit neuronsLC neuronsDopamine neuronsNucleus accumbensOptogenetic activationCellular hyperactivityPrecise circuitryStress resilienceTargeting AMPK Signaling as a Neuroprotective Strategy in Parkinson’s Disease
Curry DW, Stutz B, Andrews ZB, Elsworth JD. Targeting AMPK Signaling as a Neuroprotective Strategy in Parkinson’s Disease. Journal Of Parkinson’s Disease 2018, 8: 161-181. PMID: 29614701, PMCID: PMC6004921, DOI: 10.3233/jpd-171296.Peer-Reviewed Original ResearchMeSH Keywordsalpha-SynucleinAMP-Activated Protein KinasesAnimalsAutophagyBrainDopaminergic NeuronsHumansNeuroprotective AgentsParkinson DiseaseSignal TransductionConceptsSerine/threonine kinaseFunction of AMPKParkinson's diseaseCellular energy balanceThreonine kinaseCellular stressorsIntracellular α-synuclein aggregatesProtein kinaseAMPK activationAMPK activityNumerous dietary supplementsPreclinical PD modelsNigrostriatal dopaminergic neuronsBroad neuroprotective effectsCell deathCommon neurodegenerative disorderAMPKΑ-synuclein aggregatesNeuroprotective treatmentNeuroprotective strategiesNeuroprotective effectsNeuronal atrophyPD patientsDopaminergic neuronsKinaseAdolescent Nicotine Exposure Alters GABAA Receptor Signaling in the Ventral Tegmental Area and Increases Adult Ethanol Self-Administration
Thomas A, Ostroumov A, Kimmey B, Taormina M, Holden W, Kim K, Brown-Mangum T, Dani J. Adolescent Nicotine Exposure Alters GABAA Receptor Signaling in the Ventral Tegmental Area and Increases Adult Ethanol Self-Administration. Cell Reports 2018, 23: 68-77. PMID: 29617674, PMCID: PMC5983379, DOI: 10.1016/j.celrep.2018.03.030.Peer-Reviewed Original ResearchConceptsVentral tegmental areaAdolescent nicotine exposureNicotine exposureTegmental areaChloride extrusionLateral ventral tegmental areaSubsequent ethanol intakeVTA GABA neuronsNicotine-treated animalsGlucocorticoid receptor activationGABAA Receptor SignalingEthanol Self‐AdministrationGABA neuronsPathological drinkingVTA GABAAlcohol drinkingEthanol intakeReceptor activationSelf-AdministrationRisk profileGABANeuron responsesAdolescent smokingReceptor signalingReversal potential
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