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
PPARγ/PGC1α signaling as a potential therapeutic target for mitochondrial biogenesis in neurodegenerative disorders
Jamwal S, Blackburn J, Elsworth JD. PPARγ/PGC1α signaling as a potential therapeutic target for mitochondrial biogenesis in neurodegenerative disorders. Pharmacology & Therapeutics 2020, 219: 107705. PMID: 33039420, PMCID: PMC7887032, DOI: 10.1016/j.pharmthera.2020.107705.Peer-Reviewed Original ResearchConceptsNeurodegenerative disordersParkinson's diseaseAlzheimer's diseaseParaoxonase 2Mitochondrial biogenesisNeurodegenerative diseasesHuntington's diseasePeroxisome proliferator-activated receptorProliferator-activated receptorPotential therapeutic targetDevastating neurological disorderFunction of neuronsPeroxisome proliferator-activated receptor gamma co-activator-1 alphaPharmacological-based therapiesSymptomatic treatmentCurrent therapiesClinical trialsLigand-inducible transcription factorsTherapeutic targetNeurological disordersDiseasePPARγ modulatorsProgressive lossMitochondrial dysfunctionPromising targetGeneration 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 experimentsPioglitazone 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
2009
Dopamine
Elsworth J, Roth R. Dopamine. 2009, 539-547. DOI: 10.1016/b978-008045046-9.00683-5.Peer-Reviewed Original ResearchCo-localized peptidesDA neuron activityDopamine cell groupsDendritic spine synapsesDifferent firing patternsSpine densityDA neurotransmissionSpine synapsesParkinson's diseaseNeuron activityVolume transmissionPharmacological perspectiveCell groupsFiring patternsEndogenous mechanismsDiseaseAutoreceptorsNeurotransmissionSchizophreniaBrainSynapses
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
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 systemEstrogenDiseaseNeurons
1999
Chapter 12 Fetal Grafts in Parkinson's Disease Primate Models
Sladek J, Collier T, Elsworth J, Roth R, Taylor J, Redmond D. Chapter 12 Fetal Grafts in Parkinson's Disease Primate Models. 1999, 321-364. DOI: 10.1016/b978-012705070-6/50013-5.Peer-Reviewed Original ResearchDisease patientsFetal tissue graftsParkinson's disease patientsProgressive neurological disorderEntire striatumParkinsonian symptomsFetal graftsClinical benefitDopaminergic neuronsSubstantia nigraClinical trialsNeurosurgical interventionPrimate modelParkinson's diseaseTissue graftDonor tissueNeurological disordersSource of cellsNeurodegenerative disordersFunctional changesProgressive lossHuman embryonic tissuesOptimal ageGraftSingle donor
1998
In vivo expression of therapeutic human genes for dopamine production in the caudates of MPTP-treated monkeys using an AAV vector
During M, Samulski R, Elsworth J, Kaplitt M, Leone P, Xiao X, Li J, Freese A, Taylor J, Roth R, Sladek J, O’Malley K, Redmond D. In vivo expression of therapeutic human genes for dopamine production in the caudates of MPTP-treated monkeys using an AAV vector. Gene Therapy 1998, 5: 820-827. PMID: 9747462, DOI: 10.1038/sj.gt.3300650.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAnimalsAromatic-L-Amino-Acid DecarboxylasesChlorocebus aethiopsDependovirusDopamineDopamine AgentsGene ExpressionGene Transfer TechniquesGenetic VectorsHumansImmunohistochemistryMaleParkinson DiseaseTrigeminal Caudal NucleusTyrosine 3-MonooxygenaseConceptsTyrosine hydroxylaseStriatal cellsDopamine-depleted monkeysAdeno-associated virus vectorProduction of dopamineParkinsonian monkeysTransient feverSevere hyperactivityStriatal dopaminePrimate neuronsStereotactic injectionHistological evidencePrimate modelInjection tractNeurotoxin MPTPDopamine productionParkinson's diseaseTreatment groupsSignificant toxicityBehavioral effectsVivo gene therapyElevated levelsBiochemical effectsFirst dayMonkeys
1997
Severe long-term 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the vervet monkey (Cercopithecus aethiops sabaeus)
Taylor J, Elsworth J, Roth R, Sladek J, Redmond D. Severe long-term 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the vervet monkey (Cercopithecus aethiops sabaeus). Neuroscience 1997, 81: 745-755. PMID: 9316026, DOI: 10.1016/s0306-4522(97)00214-5.Peer-Reviewed Original ResearchConceptsParkinson's diseaseSevere parkinsonismAdult male African green monkeysMale African green monkeysTetrahydropyridine-induced parkinsonismMPTP-induced parkinsonismIdiopathic Parkinson's diseaseNovel therapeutic treatmentsLong-term deficitsAfrican green monkeysGroups of animalsNon-human primatesMPTP treatmentParkinsonian monkeysMPTP administrationVervet monkeysFunctional deficitsInitial severityStable parkinsonismBehavioral deficitsAnimal modelsParkinsonismParkinsonian subjectsMPTPTherapeutic treatmentDopamine Synthesis, Uptake, Metabolism, and Receptors: Relevance to Gene Therapy of Parkinson's Disease
Elsworth J, Roth R. Dopamine Synthesis, Uptake, Metabolism, and Receptors: Relevance to Gene Therapy of Parkinson's Disease. Experimental Neurology 1997, 144: 4-9. PMID: 9126143, DOI: 10.1006/exnr.1996.6379.Peer-Reviewed Original Research
1995
General Cognitive Ability Following Unilateral and Bilateral Fetal Ventral Mesencephalic Tissue Transplantation for Treatment of Parkinson's Disease
Sass K, Buchanan C, Westerveld M, Marek K, Farhi A, Robbins R, Naftolin F, Vollmer T, Leranth C, Roth R, Price L, Bunney B, Elsworth J, Hoffer P, Redmond D, Spencer D. General Cognitive Ability Following Unilateral and Bilateral Fetal Ventral Mesencephalic Tissue Transplantation for Treatment of Parkinson's Disease. JAMA Neurology 1995, 52: 680-686. PMID: 7619024, DOI: 10.1001/archneur.1995.00540310050016.Peer-Reviewed Original ResearchConceptsCognitive abilitiesNonverbal cognitive abilityVerbal cognitive abilityInformation-processing speedVerbal memoryNeuropsychological profileTest batteryCognitive functionNormal cognitive functionCognitive dysfunctionRight caudate nucleusCaudate nucleusFactor analysisTissue transplantationParkinson's diseaseCo-Grafts in Dopamine-Depleted Primates: Preliminary Results and Theoretical Issues Related to Human Applications for Parkinson’s Disease
Sladek J, Elsworth J, Roth R, Blanchard B, Taylor J, Collier T, Redmond D. Co-Grafts in Dopamine-Depleted Primates: Preliminary Results and Theoretical Issues Related to Human Applications for Parkinson’s Disease. Altschul Symposia Series 1995, 219-230. DOI: 10.1007/978-1-4615-1929-4_18.Peer-Reviewed Original ResearchDopamine neuronsDisease patientsHuman dopamine neuronsNon-dopaminergic neuronsVentral mesencephalic graftsParkinson's disease patientsMesencephalic reticular formationHuman neural tissueDaily levodopaHost brainMesencephalic graftsMesencephalic tissueDorsal rapheVentral mesencephalonPatient 1Serotonergic neuronsVentral tegmentumPoor survivalEmbryonic mesencephalonReticular formationTrochlear nucleusRat brainRat striatumTrigeminal complexParkinson's disease
1993
Neural Transplantation for Neurodegenerative Diseases: Past, Present, and Futurea
REDMOND D, ROTH R, SPENCER D, NAFTOLIN F, LERANTH C, ROBBINS R, MAREK K, ELSWORTH J, SASS K, TAYLOR J, SLADEK J. Neural Transplantation for Neurodegenerative Diseases: Past, Present, and Futurea. Annals Of The New York Academy Of Sciences 1993, 695: 258-266. PMID: 8239293, DOI: 10.1111/j.1749-6632.1993.tb23064.x.Peer-Reviewed Original ResearchConceptsNeural transplantationParkinson's diseaseDopamine neuronsCellular replacementClinical treatmentFetal cellsNeural tissue transplantsNeural tissueIdiopathic Parkinson's diseaseDopamine-producing cellsFunctional effectsBest medical treatmentFetal neural tissueImportant functional effectsHuman neural tissueEssential neuromodulatorDrug therapyIdiopathic diseaseClinical conditionsTherapeutic experimentsBrain cellsIneffective treatmentMedical treatmentTissue transplantsTransplantationUnilateral Transplantation of Human Fetal Mesencephalic Tissue Into the Caudate Nucleus of Patients With Parkinson's Disease
SPENCER D, ROBBINS R, NAFTOLIN F, MAREK K, VOLLMER T, LERANTH C, ROTH R, PRICE L, GJEDDE A, BUNNEY B, SASS K, ELSWORTH J, KIER E, MAKUCH R, HOFFER P, REDMOND D. Unilateral Transplantation of Human Fetal Mesencephalic Tissue Into the Caudate Nucleus of Patients With Parkinson's Disease. Obstetrical & Gynecological Survey 1993, 48: 413-415. DOI: 10.1097/00006254-199306000-00013.Peer-Reviewed Original Research
1992
Unilateral Transplantation of Human Fetal Mesencephalic Tissue into the Caudate Nucleus of Patients with Parkinson's Disease
Spencer D, Robbins R, Naftolin F, Marek K, Vollmer T, Leranth C, Roth R, Price L, Gjedde A, Bunney B, Sass K, Elsworth J, Kier E, Makuch R, Hoffer P, Redmond D. Unilateral Transplantation of Human Fetal Mesencephalic Tissue into the Caudate Nucleus of Patients with Parkinson's Disease. New England Journal Of Medicine 1992, 327: 1541-1548. PMID: 1435880, DOI: 10.1056/nejm199211263272201.Peer-Reviewed Original ResearchMeSH KeywordsActivities of Daily LivingAdultAntiparkinson AgentsCaudate NucleusCryopreservationCyclosporineDopamineFemaleFetal Tissue TransplantationHomovanillic AcidHumansMagnetic Resonance ImagingMaleMesencephalonMiddle AgedMotor ActivityParkinson DiseasePutamenStereotaxic TechniquesTomography, Emission-ComputedConceptsCase patientsParkinson's diseaseMesencephalic tissueCaudate nucleusHuman fetal ventral mesencephalic tissueFetal ventral mesencephalic tissueHuman fetal mesencephalic tissueContinued disease progressionFetal dopaminergic neuronsFetal mesencephalic tissueVentral mesencephalic tissueSevere Parkinson's diseaseOptimal drug therapySigns of parkinsonismMidbrain dopamine neuronsPositron emission tomographyMonths of evaluationAntiparkinsonian medicationUnilateral transplantationDrug holidayMore medicationsStriatonigral degenerationNeurologic functionDopaminergic neuronsDrug therapy
1991
Grafting of fetal substantia nigra to striatum reverses behavioral deficits induced by MPTP in primates: a comparison with other types of grafts as controls
Taylor J, Elsworth J, Roth R, Sladek J, Collier T, Redmond D. Grafting of fetal substantia nigra to striatum reverses behavioral deficits induced by MPTP in primates: a comparison with other types of grafts as controls. Experimental Brain Research 1991, 85: 335-348. PMID: 1893983, DOI: 10.1007/bf00229411.Peer-Reviewed Original ResearchConceptsCaudate nucleusBehavioral deficitsHealthy behaviorsFetal substantia nigra cellsFetal substantia nigraIdiopathic Parkinson's diseasePoverty of movementType of graftDays/weekSubstantia nigra cellsTime of sacrificePre-treatment levelsSN cellsSpecific behavioral effectsMPTP treatmentMPTP toxicityParkinsonian signsSubstantia nigraControl subjectsInitiation of movementBrain sitesLimb tremorParkinson's diseaseControl animalsMPTP