Ca2+ Stimulated Adenylyl Cyclases and Neuroplasticity
Ca2 刺激的腺苷酸环化酶和神经可塑性
基本信息
- 批准号:7192401
- 负责人:
- 金额:$ 33.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1984
- 资助国家:美国
- 起止时间:1984-04-01 至 2009-02-28
- 项目状态:已结题
- 来源:
- 关键词:Adenylate CyclaseAffectAftercareAlzheimer&aposs DiseaseAreaAttenuatedAutistic DisorderBiological AssayBrain-Derived Neurotrophic FactorCREB-binding proteinCREB1 geneCalmodulinCalpainCampingCatalytic DomainChromosome PairingCircadian RhythmsCognition DisordersCollaborationsCuesCyclic AMPCyclic AMP Response ElementCyclic AMP-Dependent Protein KinasesDNA Microarray ChipDNA Microarray formatDataDefectDepressed moodEndopeptidasesEventExhibitsFeedbackFigs - dietaryFundingGene FamilyGenesGenetic TranscriptionHippocampus (Brain)HumanKineticsLacZ GenesLeadLearningLong-Term PotentiationMediatingMemoryMemory LossMental RetardationMicroarray AnalysisMitogen-Activated Protein KinasesMolecularMonitorMouse StrainsMusMutant Strains MiceN-MethylaspartateNMDA receptor antagonistNeuronal PlasticityNeuronsNuclearNuclear TranslocationNumbersOligonucleotidesPathway interactionsPeptide HydrolasesPhasePhosphorylationPhosphotransferasesPlayProcessProtein KinaseProteinsRas InhibitorRegulationRelative (related person)ReporterReportingRoleSignal TransductionSignal Transduction PathwaySliceStimulusSynapsesTrainingTransgenic MiceWeekWild Type Mouseage relatedbaseconditioned feardaydentate gyrusgenetic regulatory proteinhuman CREBBP proteininsightinterestlong term memorynovelpituitary adenylate cyclase activating polypeptideprotein degradationras Guanine Nucleotide Exchange Factorsresearch study
项目摘要
DESCRIPTION (provided by applicant): There is considerable interest in the cellular and molecular basis of memory formation. Studies of learning and memory are of fundamental importance for a better understanding of cognitive disorders in humans including Alzheimer's, autism, aging-related memory loss, and various types of mental retardation. It is the general hypothesis of this proposal that Ca2+ stimulation of the CREB/CRE (cAMP response element)-transcriptional pathway plays a pivotal role in long-lasting, long-term potentiation (L-LTP) and some forms of hippocampus-dependent long-term memory (LTM). Our long-term objectives are to define the mechanisms for Ca2+ stimulation of CRE-mediated transcription in hippocampal neurons and to understand why activation of this pathway is important for LTM and L-LTP. We hypothesize that Ca2+ activation of CRE-mediated transcription requires coactivation of the Erk/MAPK and camp signal transduction pathways. We propose that the critical cAMP signal increase originates from activation of calmodulin-stimulated adenylyl cyclases. We hypothesize that cAMP signaling is required for the nuclear translocation of Erk/MAPK and may also contribute to Ca2+ activation of Erk/MAPK. We also propose that proteolytic degradation of SCOP, a Ras inhibitor, may contribute to Ca2+ activation and sensitization of the Erk/MAPK signal transduction pathway. We hypothesize that long-lasting increases in CRE-mediated transcription, or transcriptional oscillations, in the hippocampus may be due to increased expression of gene products that function as positive-feedback regulators of the Erk/MAPK/CRE transcriptional pathway.
描述(申请人提供):对记忆形成的细胞和分子基础有相当大的兴趣。对学习和记忆的研究对于更好地了解人类的认知障碍,包括阿尔茨海默氏症、自闭症、与衰老相关的记忆丧失和各种类型的精神发育迟缓具有重要的意义。这一假设的基本假设是,钙离子刺激CREB/CRE(cAMP反应元件)转录通路在长时程增强(L-LTP)和某些形式的海马区依赖的长时程记忆(LTM)中起着关键作用。我们的长期目标是明确钙离子刺激Cre介导的海马神经元转录的机制,并了解为什么这一途径的激活对LTM和L LTP具有重要意义。我们推测,钙激活Cre介导的转录需要ERK/MAPK和cAMP信号转导通路的共同激活。我们认为,关键的cAMP信号增加起源于钙调素刺激的腺酰环化酶的激活。我们推测,cAMP信号是ERK/MAPK核转位所必需的,也可能参与了ERK/MAPK的钙激活。我们还认为,Ras抑制剂SCOP的蛋白降解可能有助于激活和敏化Erk/MAPK信号转导通路。我们假设,海马区Cre介导的转录或转录振荡的长期增加可能是由于作为Erk/MAPK/Cre转录途径的正反馈调节因子的基因产物表达增加所致。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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DANIEL R STORM其他文献
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{{ truncateString('DANIEL R STORM', 18)}}的其他基金
Role of PI3 Kinase and MAP Kinase in Memory Retrieval
PI3 激酶和 MAP 激酶在记忆检索中的作用
- 批准号:
7620032 - 财政年份:2008
- 资助金额:
$ 33.24万 - 项目类别:
Role of PI3 Kinase and MAP Kinase in Memory Retrieval
PI3 激酶和 MAP 激酶在记忆检索中的作用
- 批准号:
8037101 - 财政年份:2008
- 资助金额:
$ 33.24万 - 项目类别:
Role of PI3 Kinase and MAP Kinase in Memory Retrieval
PI3 激酶和 MAP 激酶在记忆检索中的作用
- 批准号:
8240050 - 财政年份:2008
- 资助金额:
$ 33.24万 - 项目类别:
Role of PI3 Kinase and MAP Kinase in Memory Retrieval
PI3 激酶和 MAP 激酶在记忆检索中的作用
- 批准号:
7522246 - 财政年份:2008
- 资助金额:
$ 33.24万 - 项目类别:
Role of PI3 Kinase and MAP Kinase in Memory Retrieval
PI3 激酶和 MAP 激酶在记忆检索中的作用
- 批准号:
7795683 - 财政年份:2008
- 资助金额:
$ 33.24万 - 项目类别:
Memory Enhancement by A Genetic Increase in cAMP Signals
通过 cAMP 信号的遗传增强增强记忆
- 批准号:
7048100 - 财政年份:2006
- 资助金额:
$ 33.24万 - 项目类别:
Memory Enhancement by a Genetic Increase in cAMP Signals
cAMP 信号基因增加可增强记忆
- 批准号:
8786106 - 财政年份:2006
- 资助金额:
$ 33.24万 - 项目类别:
Memory Enhancement by A Genetic Increase in cAMP Signals
通过 cAMP 信号的遗传增强增强记忆
- 批准号:
7764779 - 财政年份:2006
- 资助金额:
$ 33.24万 - 项目类别:
Memory Enhancement by A Genetic Increase in cAMP Signals
通过 cAMP 信号的遗传增强增强记忆
- 批准号:
7579802 - 财政年份:2006
- 资助金额:
$ 33.24万 - 项目类别:
Memory Enhancement by a Genetic Increase in cAMP Signals
cAMP 信号基因增加可增强记忆
- 批准号:
8401162 - 财政年份:2006
- 资助金额:
$ 33.24万 - 项目类别:
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