2025
CCL21-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 deficits
2024
F91. MAPPING THE EFFECTS OF OPIOID USE DISORDER GENETIC ASSOCIATED VARIANTS IN BRAIN PATHWAYS AT A SINGLE CELL LEVEL
Rivera-Hernández M, Martínez-Magaña J, Brennand K, Montalvo-Ortiz J. F91. MAPPING THE EFFECTS OF OPIOID USE DISORDER GENETIC ASSOCIATED VARIANTS IN BRAIN PATHWAYS AT A SINGLE CELL LEVEL. European Neuropsychopharmacology 2024, 87: 254. DOI: 10.1016/j.euroneuro.2024.08.502.Peer-Reviewed Original ResearchOpioid use disorderDopaminergic neuronsReward-related learningOrbital frontal cortexGenetic variantsFunction of dopaminergic neuronsMap genetic variantsGenome-wide studiesCell projection organizationSingle-cell expression profilesCell typesOxytocin signaling pathwayPrefrontal cortexMotivated behaviorFrontal cortexDopaminergic pathwaysUse disorderBrain regionsModulation of chemical synaptic transmissionStriatumSingle-cell RNAseqCell-specific pathwaysBehavioral responsesScRNA-seqStriatum cellsParkinsonism 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(4UbiquitinEndocytosisIntense exercise increases dopamine transporter and neuromelanin concentrations in the substantia nigra in Parkinson’s disease
de Laat B, Hoye J, Stanley G, Hespeler M, Ligi J, Mohan V, Wooten D, Zhang X, Nguyen T, Key J, Colonna G, Huang Y, Nabulsi N, Patel A, Matuskey D, Morris E, Tinaz S. Intense exercise increases dopamine transporter and neuromelanin concentrations in the substantia nigra in Parkinson’s disease. Npj Parkinson's Disease 2024, 10: 34. PMID: 38336768, PMCID: PMC10858031, DOI: 10.1038/s41531-024-00641-1.Peer-Reviewed Original ResearchDopamine transporterSubstantia nigraDopaminergic neuronsDopamine transporter availabilityNeuroprotective effects of exerciseDopaminergic systemClinical progression of PDEarly PDSubstantiaNeuromelanin contentNigraLoss of dopaminergic neuronsEffects of exerciseNM-MRIDopamineSystem of patientsProgressive loss of dopaminergic neuronsParkinson's diseaseClinical progressionProgression of PDNeuroprotective effectsClinical trialsIntensity exercisePET imagingProgressive loss
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 ResearchConceptsMedial 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 ResearchConceptsAdaptive 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
Expression of PON2 isoforms varies among brain regions in male and female African green monkeys
Jamwal S, Blackburn JK, Elsworth JD. Expression of PON2 isoforms varies among brain regions in male and female African green monkeys. Free Radical Biology And Medicine 2021, 178: 215-218. PMID: 34890766, PMCID: PMC8760629, DOI: 10.1016/j.freeradbiomed.2021.12.005.Peer-Reviewed Original ResearchConceptsAfrican green monkeysParkinson's diseaseBrain regionsParaoxonase 2Different brain regionsFemale monkeysGreen monkeysPON2 expressionOxidative stress-related neurodegenerative disordersFemale African green monkeysNeurodegenerative disordersMale African green monkeysOxidative stressPON2 protein expressionAnti-inflammatory propertiesExpression levelsSignificant differencesBrain tissue samplesDorsolateral prefrontal cortexNeuroprotective strategiesWestern blotting techniquesDopaminergic neuronsPON2 proteinPrimate brainProtective roleSynaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson’s Disease
Raval NR, Gudmundsen F, Juhl M, Andersen IV, Speth N, Videbæk A, Petersen IN, Mikkelsen JD, Fisher PM, Herth MM, Plavén-Sigray P, Knudsen GM, Palner M. Synaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson’s Disease. Frontiers In Synaptic Neuroscience 2021, 13: 715811. PMID: 34867258, PMCID: PMC8636601, DOI: 10.3389/fnsyn.2021.715811.Peer-Reviewed Original ResearchNeuronal metabolic functionPositron emission tomographyParkinson's diseaseSynaptic densityCortical regionsJ bindingDopaminergic lesionVentral midbrainEmission tomographyIpsilateral ventral midbrainLower synaptic densityRostral substantia nigraUnilateral dopaminergic lesionNon-motor symptomsThalamo-cortical circuitsMetabolic functionsMedial forebrain bundleHigh synaptic densityMedial prefrontal cortexCerebral changesMotor dysfunctionUnilateral injectionDopaminergic neuronsSubstantia nigraBasal gangliaInduction 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 ResearchConceptsInduced 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 populationsThe factors for the early and late development of midbrain dopaminergic neurons segregate into two distinct evolutionary clusters
Niu Y, Moghimyfiroozabad S, Moghimyfiroozabad A, Tierney T, Alavian K. The factors for the early and late development of midbrain dopaminergic neurons segregate into two distinct evolutionary clusters. Brain Disorders 2021, 1: 100002. DOI: 10.1016/j.dscb.2021.100002.Peer-Reviewed Original ResearchTranscription factorsNon-canonical functionsMidbrain dopaminergic neuronsDistinct evolutionary pathwaysEntire human proteomeNovel molecular connectionDopaminergic neuronsPotential novel linkPhylogenetic profilesEvolutionary pathwaysHuman proteomeEvolutionary scenarioMolecular connectionEvolutionary clustersDevelopmental pathwaysNovel linkNeuronal differentiationNovel linkageDevelopmental cascadeParkinson's diseasePathwayNeuronsMotor behaviorControl of emotionsProteomeDopaminergic 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 ResearchConceptsDopaminergic 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
KTN1 Variants Underlying Putamen Gray Matter Volumes and Parkinson’s Disease
Mao Q, Wang X, Chen B, Fan L, Wang S, Zhang Y, Lin X, Cao Y, Wu YC, Ji J, Xu J, Zheng J, Zhang H, Zheng C, Chen W, Cheng W, Luo X, Wang K, Zuo L, Kang L, Li CR, Luo X. KTN1 Variants Underlying Putamen Gray Matter Volumes and Parkinson’s Disease. Frontiers In Neuroscience 2020, 14: 651. PMID: 32655362, PMCID: PMC7324786, DOI: 10.3389/fnins.2020.00651.Peer-Reviewed Original ResearchPutamen gray matter volumesSubstantia nigra pars compactaGray matter volumeParkinson's diseaseMRNA expressionSingle nucleotide polymorphismsPD riskIndependent cohortMatter volumeDevelopment of PDPars compactaDopaminergic neuronsPutamenPutamen volumeSignificant associationPD associationsRisk allelesDiseaseSelective lossCohortGene variantsA Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids
Yang L, Han Y, Nilsson-Payant BE, Gupta V, Wang P, Duan X, Tang X, Zhu J, Zhao Z, Jaffré F, Zhang T, Kim TW, Harschnitz O, Redmond D, Houghton S, Liu C, Naji A, Ciceri G, Guttikonda S, Bram Y, Nguyen DT, Cioffi M, Chandar V, Hoagland DA, Huang Y, Xiang J, Wang H, Lyden D, Borczuk A, Chen HJ, Studer L, Pan FC, Ho DD, tenOever BR, Evans T, Schwartz RE, Chen S. A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids. Cell Stem Cell 2020, 27: 125-136.e7. PMID: 32579880, PMCID: PMC7303620, DOI: 10.1016/j.stem.2020.06.015.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionHuman disease-relevant cellsSARS-CoV-2 tropismCOVID-19 pathophysiologyExpression of chemokinesRecent clinical studiesHuman pancreatic beta cellsCOVID-19SARS-CoV-2Pancreatic beta cellsLiver organoidsPancreatic endocrine cellsRespiratory failureDopaminergic neuronsClinical studiesPrimary human isletsVirus infectionAutopsy samplesBeta cellsHuman isletsEndocrine cellsOrgan systemsInfectionCholangiocyte organoidsDisease-relevant cellsImplications of the Gut Microbiome in Parkinson's Disease
Elfil M, Kamel S, Kandil M, Koo BB, Schaefer SM. Implications of the Gut Microbiome in Parkinson's Disease. Movement Disorders 2020, 35: 921-933. PMID: 32092186, DOI: 10.1002/mds.28004.Peer-Reviewed Original ResearchConceptsParkinson's disease patientsDisease patientsParkinson's diseaseMotor symptomsNervous systemEnteric nervous systemGut microbiome dysbiosisGut microbiome changesDifferent body systemsRelease of neurotoxinsCentral nervous systemCommon neurodegenerative disorderNormal gut microbiomeΑ-synuclein aggregatesNonmotor manifestationsAutoimmune responseNeuroprotective factorsAutopsy studyDopaminergic neuronsSubstantia nigraPathophysiologic changesMicrobiome dysbiosisMotor featuresGastrointestinal systemSystemic circulationLoss of MINAR2 impairs motor function and causes Parkinson’s disease-like symptoms in mice
Ho R, Amraei R, De La Cena K, Sutherland E, Mortazavi F, Stein T, Chitalia V, Rahimi N. Loss of MINAR2 impairs motor function and causes Parkinson’s disease-like symptoms in mice. Brain Communications 2020, 2: fcaa047. PMID: 32954300, PMCID: PMC7425422, DOI: 10.1093/braincomms/fcaa047.Peer-Reviewed Original ResearchReceptor 2Parkinson's spectrum disordersDisease-like symptomsPars compactaΑ-synuclein protein expressionTyrosine hydroxylase-positive neuronsSubstantia nigra pars compactaFrontal lobe brainParkinson's disease-like symptomsLewy body dementiaImpairs motor functionSevere motor deficitsPrimary clinical symptomsReceptor 2 expressionKnockout mouse brainMotor control impairmentsSpectrum disorderCommon human neurodegenerative diseasesΑ-synuclein aggregationMotor deficitsClinical symptomsDopaminergic neuronsSpontaneous locomotorClinical hallmarkMotor function
2019
Dopamine fuels its own release
Chen R, Jonas EA. Dopamine fuels its own release. Nature Neuroscience 2019, 23: 1-2. PMID: 31844312, DOI: 10.1038/s41593-019-0563-4.Peer-Reviewed Original ResearchDeletion 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 diseaseFTY720 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 microgliaPost mortem examination of Parkinson's disease brains suggests decline in mitochondrial biomass, reversed by deep brain stimulation of subthalamic nucleus
Mallach A, Weinert M, Arthur J, Gveric D, Tierney TS, Alavian KN. Post mortem examination of Parkinson's disease brains suggests decline in mitochondrial biomass, reversed by deep brain stimulation of subthalamic nucleus. The FASEB Journal 2019, 33: 6957-6961. PMID: 30862197, DOI: 10.1096/fj.201802628r.Peer-Reviewed Original ResearchConceptsDeep brain stimulationParkinson's disease brainSubthalamic nucleusParkinson's diseaseDisease brainBrain stimulationPresynaptic terminalsSNpc neuronsEffects of DBSLong-term clinical benefitSubstantia nigra pars compactaLate-stage patientsMitochondrial biomassDA neuronsSTN-DBSSurgical treatmentNeuroprotective effectsPars compactaClinical benefitDA projectionsPD brainsDopaminergic neuronsDBS treatmentNeuromodulatory effectsPD casesCortical column and whole-brain imaging with molecular contrast and nanoscale resolution
Gao R, Asano SM, Upadhyayula S, Pisarev I, Milkie DE, Liu TL, Singh V, Graves A, Huynh GH, Zhao Y, Bogovic J, Colonell J, Ott CM, Zugates C, Tappan S, Rodriguez A, Mosaliganti KR, Sheu SH, Pasolli HA, Pang S, Xu CS, Megason SG, Hess H, Lippincott-Schwartz J, Hantman A, Rubin GM, Kirchhausen T, Saalfeld S, Aso Y, Boyden ES, Betzig E. Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution. Science 2019, 363 PMID: 30655415, PMCID: PMC6481610, DOI: 10.1126/science.aau8302.Peer-Reviewed Original ResearchConceptsDopaminergic neuronsDendritic spinesMouse cortexPresynaptic densitySynaptic proteinsBrain regionsLarge-scale studiesCortical columnsLattice light-sheet microscopyNeural activityNeural developmentSpecific molecular constituentsBrainLight-sheet microscopyDegree of stereotypyNanoscale spatial relationshipExpansion microscopy
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply