2023
Age-associated sex difference in the expression of mitochondria-based redox sensitive proteins and effect of pioglitazone in nonhuman primate brain
Jamwal S, Blackburn J, Elsworth J. Age-associated sex difference in the expression of mitochondria-based redox sensitive proteins and effect of pioglitazone in nonhuman primate brain. Biology Of Sex Differences 2023, 14: 65. PMID: 37770961, PMCID: PMC10540392, DOI: 10.1186/s13293-023-00551-6.Peer-Reviewed Original ResearchConceptsSubstantia nigraSex-dependent expressionPrimate brainAdult male monkeysCerebrospinal fluidMale monkeysPeroxisome proliferator-activated receptor gamma agonistProliferator-activated receptor gamma agonistsEffect of pioglitazoneWeeks of treatmentReceptor gamma agonistsGreater expressionAdult female monkeysNonhuman primate brainNovel neuroprotective treatmentAfrican green monkeysSex-based differencesOral pioglitazoneNeuroprotective treatmentPIO treatmentRisk factorsCNS disordersGamma agonistsPreclinical studiesParkinson's disease
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 rolePioglitazone transiently stimulates paraoxonase-2 expression in male nonhuman primate brain: Implications for sex-specific therapeutics in neurodegenerative disorders
Blackburn JK, Jamwal S, Wang W, Elsworth JD. Pioglitazone transiently stimulates paraoxonase-2 expression in male nonhuman primate brain: Implications for sex-specific therapeutics in neurodegenerative disorders. Neurochemistry International 2021, 152: 105222. PMID: 34767873, PMCID: PMC8712400, DOI: 10.1016/j.neuint.2021.105222.Peer-Reviewed Original ResearchConceptsPON2 expressionParkinson's diseaseParaoxonase 2Male African green monkeysShort-term animal modelsOxidative stressPeroxisome proliferator-activated receptor gammaEffect of pioglitazoneWeeks of treatmentProliferator-activated receptor gammaNonhuman primate brainParaoxonase-2 expressionRegion-dependent expressionSex-specific therapeuticsAnti-diabetic drug pioglitazoneAfrican green monkeysDorsolateral prefrontal cortexOral pioglitazonePreclinical evidenceSubstantia nigraClinical trialsPON2 mRNAAnimal modelsPioglitazonePrimate brainSex-based disparity in paraoxonase-2 expression in the brains of African green monkeys
Jamwal S, Blackburn JK, Elsworth JD. Sex-based disparity in paraoxonase-2 expression in the brains of African green monkeys. Free Radical Biology And Medicine 2021, 167: 201-204. PMID: 33722626, PMCID: PMC8096713, DOI: 10.1016/j.freeradbiomed.2021.03.003.Peer-Reviewed Original ResearchConceptsAfrican green monkeysParaoxonase 2Parkinson's diseaseBrain regionsGreen monkeysOxidative stressReactive oxygen speciesAnti-inflammatory propertiesSex-based disparitiesParaoxonase-2 expressionDifferent brain regionsNigrostriatal systemPON2 expressionDevelopment of therapeuticsNeurodegenerative disordersDiseaseProtein levelsROS levelsLower ROS levelsMitochondrial performanceSex-based variationDisordersMonkeysOxygen speciesMales
2020
Generation 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 experimentsGene therapy and immunotherapy as promising strategies to combat Huntington’s disease-associated neurodegeneration: emphasis on recent updates and future perspectives
Jamwal S, Elsworth JD, Rahi V, Kumar P. Gene therapy and immunotherapy as promising strategies to combat Huntington’s disease-associated neurodegeneration: emphasis on recent updates and future perspectives. Expert Review Of Neurotherapeutics 2020, 20: 1123-1141. PMID: 32720531, DOI: 10.1080/14737175.2020.1801424.Peer-Reviewed Original ResearchConceptsGene therapyClinical trialsDisease-modifying therapiesMutant huntingtinTreatment of HDAntibody-based therapiesPotential therapeutic interventionsNew therapeutic targetsGene-based therapiesImmune activationClinical dataImmunotherapyTherapeutic targetFunctional restorationTherapeutic interventionsTherapyHD pathogenesisMHTT proteinRecent updatesFuture perspectivesPromising strategyTrialsCurrent statusConsiderable attentionHDPioglitazone activates paraoxonase-2 in the brain: A novel neuroprotective mechanism
Blackburn JK, Curry DW, Thomsen AN, Roth RH, Elsworth JD. Pioglitazone activates paraoxonase-2 in the brain: A novel neuroprotective mechanism. Experimental Neurology 2020, 327: 113234. PMID: 32044330, PMCID: PMC7089823, DOI: 10.1016/j.expneurol.2020.113234.Peer-Reviewed Original ResearchConceptsParaoxonase 2Novel neuroprotective mechanismParaoxonase-2 expressionAnti-diabetic drug pioglitazoneReactive oxygen species productionNeuroprotective strategiesNeuroprotective mechanismsBrain traumaMouse striatumOxygen species productionParkinson's diseaseAlzheimer's diseaseTherapeutic potentialPioglitazoneDiseaseOxidative stressDrug pioglitazoneSpecies productionBrainNeuroprotectionIschemiaStriatumExpressionPathologyTrauma
2018
Human–Monkey Chimeras for Modeling Human Disease: Opportunities and Challenges
De Los Angeles A, Hyun I, Latham S, Elsworth J, Redmond D. Human–Monkey Chimeras for Modeling Human Disease: Opportunities and Challenges. Stem Cells And Development 2018, 27: 1599-1604. PMID: 30319057, PMCID: PMC7366261, DOI: 10.1089/scd.2018.0162.Peer-Reviewed Original ResearchConceptsImportant ethical considerationsModeling Human DiseaseHuman PS cellsInterspecies chimerasUse of monkeysChimera researchEthical considerationsEthical concernsInvasive researchCell researchPolitical issuesScientific valueBiomedical researchLight of advancesHuman stem cellsJurisdictionsPS cellsHoly grailQuestions
2017
Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing
Camell CD, Sander J, Spadaro O, Lee A, Nguyen KY, Wing A, Goldberg EL, Youm YH, Brown CW, Elsworth J, Rodeheffer MS, Schultze JL, Dixit VD. Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing. Nature 2017, 550: 119-123. PMID: 28953873, PMCID: PMC5718149, DOI: 10.1038/nature24022.Peer-Reviewed Original ResearchAdipocytesAdipose TissueAgingAnimalsCaspase 1CatecholaminesGene Expression ProfilingGene Expression RegulationGrowth Differentiation Factor 3InflammasomesLipaseLipolysisMacrophagesMiceMonoamine OxidaseMonoamine Oxidase InhibitorsNLR Family, Pyrin Domain-Containing 3 ProteinNorepinephrineSterol Esterase
2005
Neural Stem Cells Implanted into MPTP-Treated Monkeys Increase the Size of Endogenous Tyrosine Hydroxylase-Positive Cells Found in the Striatum: A Return to Control Measures
Bjugstad K, Redmond D, Teng Y, Elsworth J, Roth R, Blanchard B, Snyder E, Sladek J. Neural Stem Cells Implanted into MPTP-Treated Monkeys Increase the Size of Endogenous Tyrosine Hydroxylase-Positive Cells Found in the Striatum: A Return to Control Measures. Cell Transplantation 2005, 14: 183-192. PMID: 15929553, DOI: 10.3727/000000005783983098.Peer-Reviewed Original ResearchConceptsTyrosine hydroxylase-positive cellsNeural stem cellsHydroxylase-positive cellsSubstantia nigraHuman neural stem cellsParkinson's diseaseHuman NSCsCaudate nucleusEffects of NSCsPresence of NSCsImplanted neural stem cellsRight substantia nigraUntreated control monkeysRight caudate nucleusCell populationsAfrican green monkeysEndogenous cell populationsStem cellsMPTP damageMPTP treatmentStriatal environmentNigrostriatal pathwayDopamine neuronsControl monkeysSelective dopaminergic
2001
Prenatal cocaine exposure increases mesoprefrontal dopamine neuron responsivity to mild stress
Elsworth J, Morrow B, Roth R. Prenatal cocaine exposure increases mesoprefrontal dopamine neuron responsivity to mild stress. Synapse 2001, 42: 80-83. PMID: 11574943, DOI: 10.1002/syn.1102.Peer-Reviewed Original ResearchConceptsPrenatal cocaine exposurePrefrontal cortexCocaine exposureShort-term memory deficitsVentromedial prefrontal cortexShort-term memoryMedial prefrontal cortexDopamine neuronsAdolescent ratsCognitive deficitsMemory deficitsMesoprefrontal dopamine systemPrenatal cocaineMild footshock stressDopamine systemDeficitsFootshock stressNeurobehavioral deficitsDopamine turnoverIntravenous modelRodent modelsBehavioral abnormalitiesFetal developmentMild stressCortexPrenatal exposure to cocaine reduces the number and enhances reactivity of A10 dopaminergic neurons to environmental stress
Morrow B, Elsworth J, Roth R. Prenatal exposure to cocaine reduces the number and enhances reactivity of A10 dopaminergic neurons to environmental stress. Synapse 2001, 41: 337-344. PMID: 11494404, DOI: 10.1002/syn.1090.Peer-Reviewed Original ResearchConceptsA10 dopamine neuronsDopamine neuronsDopaminergic neuronsPrenatal exposurePrenatal saline controlsTyrosine hydroxylase immunoreactiveA10 dopaminergic neuronsCocaine-induced reductionRat dopaminergic neuronsCocaine-exposed ratsPoor cognitive performanceYoung adult offspringUnderlying biochemical changesDopaminergic functionA9 regionSaline controlsIntravenous modelPerinatal lossAdult offspringIntermittent footshockImmediate early genesCognitive deficitsNeuronal systemsBehavioral effectsCell groupsGlial Cell Line-Derived Neurotrophic Factor (GDNF) Gene Delivery Protects Dopaminergic Terminals from Degeneration
Connor B, Kozlowski D, Unnerstall J, Elsworth J, Tillerson J, Schallert T, Bohn M. Glial Cell Line-Derived Neurotrophic Factor (GDNF) Gene Delivery Protects Dopaminergic Terminals from Degeneration. Experimental Neurology 2001, 169: 83-95. PMID: 11312561, DOI: 10.1006/exnr.2001.7638.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAutoradiographyCarrier ProteinsCocaineCorpus StriatumDisease Models, AnimalDopamineDopamine Plasma Membrane Transport ProteinsGenetic TherapyGenetic VectorsGlial Cell Line-Derived Neurotrophic FactorMaleMembrane GlycoproteinsMembrane Transport ProteinsMicroinjectionsMotor ActivityNerve Growth FactorsNerve Tissue ProteinsNeuronsNeurotransmitter AgentsOxidopamineParkinson Disease, SecondaryPresynaptic TerminalsRatsRats, Inbred F344RNA, MessengerSubstantia NigraTyrosine 3-MonooxygenaseConceptsGlial cell line-derived neurotrophic factorGDNF gene deliverySubstantia nigraDA terminalsDA neuronsNeuronal sproutingGlial cell line-derived neurotrophic factor (GDNF) gene deliveryAmphetamine-induced rotational asymmetryLine-derived neurotrophic factorUnilateral intrastriatal injectionAged rat brainDopaminergic neuronal functionTyrosine hydroxylase mRNADA transporter ligandsNigrostriatal functionStriatal injectionAxonal sproutingDopaminergic terminalsIntrastriatal injectionStriatal denervationDenervated striatumWeeks postlesionNeurotrophic factorNigrostriatal axonsPartial lesionsNicotine Receptor Inactivation Decreases Sensitivity to Cocaine
Zachariou V, Caldarone B, Weathers-Lowin A, George T, Elsworth J, Roth R, Changeux J, Picciotto M. Nicotine Receptor Inactivation Decreases Sensitivity to Cocaine. Neuropsychopharmacology 2001, 24: 576-589. PMID: 11282258, DOI: 10.1016/s0893-133x(00)00224-4.Peer-Reviewed Original ResearchConceptsPlace preferenceDA turnoverLow doseHigh-affinity nicotinic acetylcholine receptorsMesolimbic DA systemHigh-affinity nAChRsNicotinic antagonist mecamylamineWild-type miceMesolimbic dopamine systemFos-related antigensProperties of nicotineCocaine place preferenceΒ2 subunitNicotinic acetylcholine receptorsAntagonist mecamylamineDA releaseMetabolite DOPACNeurochemical changesSubthreshold doseType miceDopamine systemPsychomotor stimulantsAcetylcholine receptorsHigh dosesBrain regions
2000
Estrogen Is Essential for Maintaining Nigrostriatal Dopamine Neurons in Primates: Implications for Parkinson's Disease and Memory
Leranth C, Roth R, Elsworth J, Naftolin F, Horvath T, Redmond D. Estrogen Is Essential for Maintaining Nigrostriatal Dopamine Neurons in Primates: Implications for Parkinson's Disease and Memory. Journal Of Neuroscience 2000, 20: 8604-8609. PMID: 11102464, PMCID: PMC6773080, DOI: 10.1523/jneurosci.20-23-08604.2000.Peer-Reviewed Original ResearchConceptsNigrostriatal dopamine neuronsDopamine neuronsParkinson's diseaseSubstantia nigraDopamine cellsTyrosine hydroxylase-expressing neuronsTyrosine hydroxylase-immunoreactive cellsNigral dopamine systemsEstrogen replacement therapyNew treatment strategiesUnbiased stereological analysisTypes of neuronsProgression of diseaseEstrogen replacementPostmenopausal womenEstrogen deprivationReplacement therapyTreatment strategiesCompact zoneGonadal hormonesLong-term effectsDopamine systemEstrogenDiseaseNeuronsTMT, a predator odor, elevates mesoprefrontal dopamine metabolic activity and disrupts short-term working memory in the rat
Morrow B, Roth R, Elsworth J. TMT, a predator odor, elevates mesoprefrontal dopamine metabolic activity and disrupts short-term working memory in the rat. Brain Research Bulletin 2000, 52: 519-523. PMID: 10974491, DOI: 10.1016/s0361-9230(00)00290-2.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexPrefrontal cortexExploratory behaviorSample taskFamiliar objectsNovel objectsMesoprefrontal dopamine neuronsTrimethylthiazolineMemoryPsychological stressTMT exposureObject recognition methodPredator odorSet of objectsCortexElevated serum corticosteroneDopaminergic inputDopaminergic activityBrief exposureDopaminergic innervationSerum corticosteroneDopamine neuronsDopamine metabolismObjectsRecognition methodThe predator odor, TMT, displays a unique, stress-like pattern of dopaminergic and endocrinological activation in the rat
Morrow B, Redmond A, Roth R, Elsworth J. The predator odor, TMT, displays a unique, stress-like pattern of dopaminergic and endocrinological activation in the rat. Brain Research 2000, 864: 146-151. PMID: 10793199, DOI: 10.1016/s0006-8993(00)02174-0.Peer-Reviewed Original ResearchConceptsDopamine metabolismSerum corticosteroneAcute exposureCentral dopamine metabolismNucleus accumbens coreMedial prefrontal cortexFear-inducing behaviorPredator odorCentral effectsAccumbens coreRatsStressful stimuliPrefrontal cortexConditioned fearAltered behaviorControl odorAversive stimuliCorticosteroneMetabolismOpen fieldBiochemical activationUnique patternExposureActivationTMTDivergent effects of putative anxiolytics on stress‐induced Fos expression in the mesoprefrontal system of the rat
Morrow B, Elsworth J, Lee E, Roth R. Divergent effects of putative anxiolytics on stress‐induced Fos expression in the mesoprefrontal system of the rat. Synapse 2000, 36: 143-154. PMID: 10767061, DOI: 10.1002/(sici)1098-2396(200005)36:2<143::aid-syn7>3.0.co;2-h.Peer-Reviewed Original ResearchConceptsVentral tegmental areaFos-LITegmental areaMedial prefrontal cortexPutative anxiolyticsBenzodiazepine agonistsStress-induced Fos-like immunoreactivityPartial agonistStress-induced Fos expressionGlycine/NMDA receptorPrefrontal cortexMesoprefrontal dopamine neuronsPutative anxiolytic agentsTH-LI cellsSaline-treated ratsFos-like immunoreactivityAnxiolytic-like actionFos-LI nucleiWeak partial agonistStress-induced increaseFear-inducing behaviorFootshock paradigmAlpha2 agonistsStress-induced activationDopaminergic neurons
1999
Striatal dopaminergic correlates of stable parkinsonism and degree of recovery in old-world primates one year after MPTP treatment
Elsworth J, Taylor J, Sladek J, Collier T, Redmond D, Roth R. Striatal dopaminergic correlates of stable parkinsonism and degree of recovery in old-world primates one year after MPTP treatment. Neuroscience 1999, 95: 399-408. PMID: 10658619, DOI: 10.1016/s0306-4522(99)00437-6.Peer-Reviewed Original ResearchConceptsHomovanillic acid/dopamine ratioMPTP treatmentStriatal dopamine levelsDopamine levelsDopamine lossDopamine depletionDopamine ratioStriatal subregionsNucleus accumbensCaudate nucleusDopamine concentrationsOne-yearSeverity categoriesDopamine neuron integrityVentromedial caudate nucleusStriatal dopamine lossHomovanillic acid concentrationsStriatal dopaminergic functionMarked increaseNormal motor performancePaucity of dataMetabolic activityNon-human primatesParkinsonian disabilityTetrahydropyridine (MPTP) modelSpontaneous Blink Rates Correlate with Dopamine Levels in the Caudate Nucleus of MPTP-Treated Monkeys
Taylor J, Elsworth J, Lawrence M, Sladek J, Roth R, Redmond D. Spontaneous Blink Rates Correlate with Dopamine Levels in the Caudate Nucleus of MPTP-Treated Monkeys. Experimental Neurology 1999, 158: 214-220. PMID: 10448434, DOI: 10.1006/exnr.1999.7093.Peer-Reviewed Original ResearchConceptsCaudate nucleusConcentration of DAEye blink rateBlink rateDA ratioDopaminergic regulationD1 agonist dihydrexidineDA D2 receptorsDopaminergic neurotoxin MPTPSeverity of parkinsonismSpontaneous eye blink rateSpecific brain regionsAntiparkinsonian effectsDA depletionD2 agonistDopamine D1Dopamine levelsNeurotoxin MPTPD2 receptorsMPTPNormal animalsRostral portionSubcortical regionsBrain regionsVentromedial region