Role of BCL-xL in synaptic plasticity in the hippocampus
Role of BCL-xL in synaptic plasticity in the hippocampus
批准号:
7781513
负责人:
Elizabeth Ann Jonas
金额:
$43.42万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-09-15 至 2011-08-31
关键词:
AcuteAdultAffectAlzheimer&aposs DiseaseApoptosisBrainCell DeathCessation of lifeChemosensitizationComplexDevelopmentDown-RegulationEventFamily memberFrequenciesGangliaHippocampus (Brain)Injection of therapeutic agentIonsLifeLong-Term PotentiationMembraneMetabolicMetabolismMitochondriaMolecularMultienzyme ComplexesMyxoid cystNervous system structureNeuronal PlasticityNeuronsOperative Surgical ProceduresOrganellesParkinson DiseasePhasePhysiologicalPlayPresynaptic TerminalsPreventionProductionProtein FamilyProteinsRecombinantsRoleSiteSliceSquidStimulusStrokeSynapsesSynaptic TransmissionSynaptic plasticityTestingVariantVesicleWhole-Cell Recordingsdesignimprovedinhibitor/antagonistknock-downmemory processneuroprotectionneurotransmissionneurotransmitter releaseoverexpressionpresynapticpreventresponsesmall hairpin RNAsmall molecule
中文摘要
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英文摘要
BCL-2 family proteins playa major role in the commitment phase of programmed cell death.
BCL-2 family proteins contribute either to the onset of cell death or to the protection against cell
death. BCL-xL is the major BCL-2 family member expressed in brain, and understanding its
function is key to designing strategies for neuroprotectlon. Levels of BCL-xL begin to rise just as
synapses are forming in the brain. BCL-xL levels remain high, however, in the adult nervous
system even in the absence of a death stimulus, prompting us to hypothesize that BCL-xL plays
an important physiological role in synaptic transmission. We have shown that recombinant BCLxL
injected into the presynaptic terminal of squid giant ganglion increases the amount of
neurotransmitter released upon a stimulus to the synapse. This action of BCL-xL is mimicked by
injection of ATP, which occludes the effects of injection of BCL-xL, suggesting that BCL-xL may
make more ATP available acutely for synaptic transmission. Furthermore, when BCL-xL is
overexpressed in cultured hippocampal neurons, it targets to mitochondria, localizes these
organelles to synapses, increases the number and size of synapses and the rate of
spontaneous neurotransmitter release events.
Short and long term potentiation of neurotransmitter release after high frequency
stimulation are well-studied phenomena that occur during development and in neural plasticity.
An important form of synaptic plasticity is long term potentiation (L TP) at the CA3-CA 1 synapse
in mammalian hippocampus. Changes induced by stimulation at this site are thought to underlie
the processes of memory formation. We have strong preliminary evidence to support the
hypothesis that BCl·xl is required for the modulation of long term potentiation of
neurotransmission at this synapse. We hypothesize and have strong evidence that one
mechanism of action of BCl·xl is to increase the formation and release of ATP by
mitochondria. In this application, we will test the concept that inhibition of BCl·xl or down
regulation of expression of BCl-xl prevents an increase in efficiency of operation of the ATP
synthase enzyme complex. We hypothesize that these changes are required for long term
changes in synaptic strength after high frequency synaptic stimulation, therefore we plan to test
whether inhibition of BCl·xl prevents l TP.
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Role of DJ1 in mitochondrial biogenergetics and neuronal metabolism
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批准号:10434136
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资助金额:$47.51万
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财政年份:2021
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依托单位:
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批准号:10276606
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批准号:10653710
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资助金额:$41.88万
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批准号:9429217
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资助金额:$22.99万
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财政年份:2017
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Role of DJ1 in mitochondrial biogenergetics and neuronal metabolism
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批准号:8743398
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资助金额:$45.79万
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财政年份:2014
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依托单位:
Role of DJ1 in mitochondrial biogenergetics and neuronal metabolism
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批准号:8812017
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资助金额:$45.05万
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财政年份:2014
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负责人:Elizabeth Ann Jonas
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依托单位:
Role of Bcl-xl in synaptic plasticity in the hippocampus
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批准号:8476413
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项目类别:
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资助金额:$38.53万
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财政年份:2009
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负责人:Elizabeth Ann Jonas
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依托单位:
THE ANTI-APOPTOTIC PROTEIN BCL-XL ENHANCES NEURONAL METABOLISM
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批准号:7953836
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项目类别:
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资助金额:$4.48万
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财政年份:2008
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负责人:Elizabeth Ann Jonas
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依托单位:
THE ANTI-APOPTOTIC PROTEIN BCL-XL ENHANCES NEURONAL METABOLISM
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批准号:7721086
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项目类别:
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资助金额:$3.38万
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财政年份:2007
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负责人:Elizabeth Ann Jonas
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依托单位:
THE ANTI-APOPTOTIC PROTEIN BCL-XL ENHANCES NEURONAL METABOLISM
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批准号:7598492
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项目类别:
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资助金额:$3.52万
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财政年份:2006
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负责人:Elizabeth Ann Jonas
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依托单位:
THE ANTI-APOPTOTIC PROTEIN BCL-XL ENHANCES NEURONAL METABOLISM
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批准号:7357338
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项目类别:
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资助金额:$3.68万
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财政年份:2005
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负责人:Elizabeth Ann Jonas
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依托单位:
Mitochondrial Ion Channels in Hypoxic Neurons
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批准号:9292381
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项目类别:
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资助金额:$41.63万
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财政年份:2004
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负责人:Elizabeth Ann Jonas
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依托单位:
Mitochondrial Ion Channels in Hypoxic Neurons
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批准号:10538628
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项目类别:
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资助金额:$42.57万
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财政年份:2004
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负责人:Elizabeth Ann Jonas
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依托单位:
Mitochondrial ion channels in hypoxic neurons
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批准号:7758289
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项目类别:
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资助金额:$35.84万
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财政年份:2004
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负责人:Elizabeth Ann Jonas
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依托单位:
Mitochondrial Ion Channels in Hypoxic Neurons
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批准号:8760518
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项目类别:
-
资助金额:$41.63万
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财政年份:2004
-
负责人:Elizabeth Ann Jonas
-
依托单位:
Mitochondrial ion channels in hypoxic neurons
-
批准号:7869511
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项目类别:
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资助金额:$30.33万
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财政年份:2004
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负责人:Elizabeth Ann Jonas
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依托单位:
Mitochondrial Ion Channels in Hypoxic Neurons
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批准号:10364107
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项目类别:
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资助金额:$49.26万
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财政年份:2004
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负责人:Elizabeth Ann Jonas
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依托单位:
Mitochondrial ion channels in hypoxic neurons
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批准号:8471504
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项目类别:
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资助金额:$34.24万
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财政年份:2004
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负责人:Elizabeth Ann Jonas
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依托单位:
Mitochondrial ion channels in hypoxic neurons
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批准号:8033195
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项目类别:
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资助金额:$35.48万
-
财政年份:2004
-
负责人:Elizabeth Ann Jonas
-
依托单位:
Mitochondrial ion channels in hypoxic neurons
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批准号:7873565
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项目类别:
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资助金额:$3.5万
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财政年份:2004
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负责人:Elizabeth Ann Jonas
-
依托单位:
海外基金