2013
The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry
Hess ME, Hess S, Meyer KD, Verhagen LA, Koch L, Brönneke HS, Dietrich MO, Jordan SD, Saletore Y, Elemento O, Belgardt BF, Franz T, Horvath TL, Rüther U, Jaffrey SR, Kloppenburg P, Brüning JC. The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry. Nature Neuroscience 2013, 16: 1042-1048. PMID: 23817550, DOI: 10.1038/nn.3449.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAlpha-Ketoglutarate-Dependent Dioxygenase FTOAnimalsCocaineCorpus StriatumDopamineDopaminergic NeuronsExploratory BehaviorFemaleG Protein-Coupled Inwardly-Rectifying Potassium ChannelsLocomotionMaleMesencephalonMethylationMethyltransferasesMiceMice, Inbred C57BLMice, KnockoutMixed Function OxygenasesOxo-Acid-LyasesPhenotypeQuinpiroleReceptors, Dopamine D2Receptors, Dopamine D3RewardRNA Processing, Post-TranscriptionalRNA, MessengerSignal Transduction
2011
GPA protects the nigrostriatal dopamine system by enhancing mitochondrial function
Horvath TL, Erion DM, Elsworth JD, Roth RH, Shulman GI, Andrews ZB. GPA protects the nigrostriatal dopamine system by enhancing mitochondrial function. Neurobiology Of Disease 2011, 43: 152-162. PMID: 21406233, PMCID: PMC3623269, DOI: 10.1016/j.nbd.2011.03.005.Peer-Reviewed Original ResearchConceptsNormal chow-fed miceNigrostriatal dopamine systemChow-fed miceTH neuronsGuanidinopropionic acidNormal chowParkinson's diseaseDopamine systemMitochondrial functionMitochondrial dysfunctionModels of neurodegenerationMitochondrial numberAMPK activityMPTP treatmentMPTP intoxicationNigrostriatal functionNeuroprotective effectsMitochondrial respirationNeuroprotective propertiesStriatal dopamineAMPK-dependent increaseDisease progressionMouse modelMiceMPTP
2009
Ghrelin Promotes and Protects Nigrostriatal Dopamine Function via a UCP2-Dependent Mitochondrial Mechanism
Andrews ZB, Erion D, Beiler R, Liu ZW, Abizaid A, Zigman J, Elsworth JD, Savitt JM, DiMarchi R, Tschöp M, Roth RH, Gao XB, Horvath TL. Ghrelin Promotes and Protects Nigrostriatal Dopamine Function via a UCP2-Dependent Mitochondrial Mechanism. Journal Of Neuroscience 2009, 29: 14057-14065. PMID: 19906954, PMCID: PMC2845822, DOI: 10.1523/jneurosci.3890-09.2009.Peer-Reviewed Original ResearchConceptsDA cell lossNigrostriatal dopamine functionParkinson's diseaseDopamine functionCell lossSubstantia nigra pars compactaSNpc DA neuronsStriatal dopamine levelsStriatal dopamine lossExogenous ghrelin administrationLoss of appetiteDopamine cell degenerationNovel therapeutic strategiesMitochondrial mechanismsTyrosine hydroxylase mRNAReactive oxygen species productionMPTP treatmentPeripheral ghrelinSNpc cellsTetrahydropyridine (MPTP) treatmentDA neuronsDopamine lossGhrelin administrationPars compactaCatecholaminergic neurons
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