Electrochemical Analysis of Dopamine Release
Electrochemical Analysis of Dopamine Release
批准号:
7415288
负责人:
Margaret E Rice
金额:
$42.25万
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-05-01 至 2008-04-30
关键词:
AMPA ReceptorsAddressAffinityAntioxidantsAxonBehaviorBrainBrain DiseasesCRSP3 geneCaviaCell physiologyCellsCharacteristicsCognitiveConditionCorpus striatum structureDataDendritesDependenceDetectionDiffuseDiseaseDopamineDorsalElevationFire - disastersFunctional disorderFundingGenerationsGlutamatesGoalsHydrogen PeroxideIon TransportIonsKnockout MiceLeadLinkMediatingMembrane PotentialsMetabolicMethodsMidbrain structureMitochondriaMotorN-Methyl-D-Aspartate ReceptorsNeuronsOxidative StressPacemakersParkinson DiseaseParkinsonian DisordersPathway interactionsPopulationPresynaptic TerminalsProductionRateReactive Oxygen SpeciesReceptor ActivationRegulationRelative (related person)ResistanceRewardsRoleSchizophreniaSignal TransductionSliceStructureSubstantia nigra structureTestingTetrodotoxinTherapeutic InterventionTimeVentral StriatumVentral Tegmental AreaWorkaddictionbrain pathwaychannel blockersdopaminergic neurondriving forcefluorescence imaginggamma-Aminobutyric Acidinsightmitochondrial membraneneuronal cell bodypars compactapreventresearch studysegregationsulfonylurea receptortransmission process
中文摘要
多巴胺(DA)是大脑运动、认知和奖赏通路的关键递质,具有功能障碍
英文摘要
Dopamine (DA) is a key transmitter in motor, cognitive, and reward pathways of the brain, with dysfunction of
DA transmission linked to significant disorders, including Parkinson's disease, schizophrenia, and addiction.
The long-term goal of this project is to identify local factors that regulate somatodendritic DA release from DA
neurons in the substantial nigra pars compacta (SNc) and ventral tegmental area (VTA) and axonal DA
release in striatum. Our previous work focused on release regulation by endogenous glutamate, GABA, and
Ca2+ entry, using real-time voltammetric recording of evoked DA release. We discovered that hydrogen
peroxide (H202), a reactive oxygen species (ROS) is in intracellular messenger in SNc DA neurons, that
both modulates cell firing rate and inhibits somatodendritic DA release. In dorsal striatum, H202 is a
diffusible messenger that mediates regulation of axonal DA release by glutamate and GABA. These effects
are mediated by H2O2-dependent activation of ATP-sensitive K+ (K-ATP) channels. Proposed work will
provide mechanistic insight into regulation of DA transmission by H202, as well as indicate functional
consequences of H2O2 signaling on somatodendritic and axonal DA release. Aim 1 will test the hypothesis
that H2O2 activates K-ATP channels by decreasing channel sensitivity to ATP; Aim 2 will determine the ionic
dependence of H2O2 generation; Aim 3 will investigate the role of H2O2 generation in reguaiton of
somatodendritic DA release and DA cell physiology by glutamatergic NMDA receptors; and Aim 4 will
evaluate the temporal and spatial characteristics of glutamate-dependent H202 signaling in dorsal striatum.
Methods include voltammetric detection of DA release, whole-cell and excised patch recording, and
fluorescence imaging of H2O2, intracellular ions, and mitochondria! potential, using transfected cells,
isolated neurons, and brain slices from guinea pigs and K-ATP channel-subunit knockout mice.
Several brain disorders that involve dopamine dysfunction, including Parkinson's disease and schizophrenia,
have also been linked to oxidative stress. Proposed studies will clarify how endogenous hydrogen peroxide
normally regulates dopamine release. Because unregulated H2O2 can lead to oxidative stress, however, the
findings may also point to possible targets for therapeutic intervention in these disorders.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Dopamine Release Regulation by Co-Released Glutamate and GABA
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批准号:9031754
-
项目类别:
-
资助金额:$39.85万
-
财政年份:2015
-
负责人:Margaret E Rice
-
依托单位:
Afterhyperpolarization in dopamine neurons, H2O2 and KATP channels
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批准号:7921292
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项目类别:
-
资助金额:$7.04万
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财政年份:2008
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负责人:Margaret E Rice
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依托单位:
Regulation of Dopamine Release by ROS
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批准号:6683194
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项目类别:
-
资助金额:$20.07万
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财政年份:2002
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负责人:Margaret E Rice
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依托单位:
Regulation of Dopamine Release by ROS
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批准号:6579833
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项目类别:
-
资助金额:$20.02万
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财政年份:2002
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负责人:Margaret E Rice
-
依托单位:
ASCORBATE AND GLUTATHIONE IN CNS INJURY
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批准号:6336719
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项目类别:
-
资助金额:$19.33万
-
财政年份:2000
-
负责人:Margaret E Rice
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依托单位:
ASCORBATE AND GLUTATHIONE IN CNS INJURY
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批准号:6205052
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项目类别:
-
资助金额:$19.33万
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财政年份:1999
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负责人:Margaret E Rice
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依托单位:
ASCORBATE AND GLUTATHIONE IN CNS INJURY
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批准号:6112550
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项目类别:
-
资助金额:$0.0万
-
财政年份:1998
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负责人:Margaret E Rice
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依托单位:
ASCORBATE AND GLUTATHIONE IN CNS INJURY
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批准号:6243843
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项目类别:
-
资助金额:$19.0万
-
财政年份:1997
-
负责人:Margaret E Rice
-
依托单位:
Electrochemical Analysis of Dopamine Release
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批准号:8132779
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项目类别:
-
资助金额:$7.25万
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财政年份:1997
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负责人:Margaret E Rice
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依托单位:
Electrochemical Analysis of Dendritic Dopamine Release
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批准号:6740204
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项目类别:
-
资助金额:$32.11万
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财政年份:1997
-
负责人:Margaret E Rice
-
依托单位:
Electrochemical Analysis of Dendritic Dopamine Release
-
批准号:7051463
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项目类别:
-
资助金额:$31.36万
-
财政年份:1997
-
负责人:Margaret E Rice
-
依托单位:
Electrochemical Analysis of Dopamine Release
-
批准号:7387955
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项目类别:
-
资助金额:$35.59万
-
财政年份:1997
-
负责人:Margaret E Rice
-
依托单位:
Electrochemical Analysis of Dopamine Release
-
批准号:7572879
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项目类别:
-
资助金额:$33.37万
-
财政年份:1997
-
负责人:Margaret E Rice
-
依托单位:
Electrochemical Analysis of Dendritic Dopamine Release
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批准号:6479639
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项目类别:
-
资助金额:$32.0万
-
财政年份:1997
-
负责人:Margaret E Rice
-
依托单位:
Electrochemical Analysis of Dopamine Release
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批准号:7843469
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项目类别:
-
资助金额:$33.04万
-
财政年份:1997
-
负责人:Margaret E Rice
-
依托单位:
Electrochemical Analysis of Dopamine Release
-
批准号:7917798
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项目类别:
-
资助金额:$3.43万
-
财政年份:1997
-
负责人:Margaret E Rice
-
依托单位:
Electrochemical Analysis of Dopamine Release
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批准号:8074370
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项目类别:
-
资助金额:$32.7万
-
财政年份:1997
-
负责人:Margaret E Rice
-
依托单位:
ELECTROCHEMICAL ANALYSIS OF DENDRITIC DOPAMINE RELEASE
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批准号:2039077
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项目类别:
-
资助金额:$23.94万
-
财政年份:1997
-
负责人:Margaret E Rice
-
依托单位:
ELECTROCHEMICAL ANALYSIS OF DENDRITIC DOPAMINE RELEASE
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批准号:6188022
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项目类别:
-
资助金额:$20.2万
-
财政年份:1997
-
负责人:Margaret E Rice
-
依托单位:
Electrochemical Analysis of Dopamine Release
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批准号:7875732
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项目类别:
-
资助金额:$8.02万
-
财政年份:1997
-
负责人:Margaret E Rice
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依托单位:
海外基金