The role of mTOR signaling in the cognitive impact of sleep deprivation
mTOR 信号传导在睡眠剥夺认知影响中的作用
基本信息
- 批准号:8717169
- 负责人:
- 金额:$ 5.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-04-01 至 2016-03-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAlzheimer&aposs DiseaseAnimalsAttenuatedBehavioral ParadigmBrainBrain regionCognitionCognitiveCognitive deficitsComplexDevelopmentExtramural ActivitiesGene ExpressionGene ProteinsGeneticHealthHippocampus (Brain)HourImpairmentLeadLearningMaintenanceMediatingMemoryMemory impairmentMental DepressionMental disordersMentorsMolecularNeurodegenerative DisordersNeuronsPathway interactionsPersonal SatisfactionPhosphorylationPlayPreparationProtein BiosynthesisProteinsPublic HealthPublishingQuality of lifeResearchRibosomal Protein S6 KinaseRoleSchizophreniaSignal PathwaySignal TransductionSleepSleep DeprivationSocietiesSynaptic plasticityTechniquesTestingTimeTrainingTranslation InitiationTranslationsViralWorkbasecareercareer developmentcell typemTOR proteinmutantnovelnovel therapeutic interventionpublic health relevanceresearch studytool
项目摘要
DESCRIPTION (provided by applicant): Sleep loss produces deficits in hippocampal synaptic plasticity and hippocampus-dependent memory storage. However, the molecular and cellular mechanisms that underlie these effects of sleep deprivation remain unclear. Several studies have suggested that protein synthesis pathways are altered during sleep and after periods of sleep deprivation. None however have previously described in mechanistic detail how protein synthesis is altered with sleep or sleep deprivation, nor how these alterations regulate memory formation. In this proposal, we will explore the protein synthesis regulatory role of mammalian target of rapamycin (mTOR) signaling during sleep and sleep-mediated memory consolidation. The experiments proposed will develop tools to analyze mTOR signaling in the brain and will provide direct evidence for a novel role of mTOR signaling in sleep-dependent memory consolidation. In this application, two Specific Aims are proposed that use novel genetic approaches to study how sleep deprivation affects the mTOR signaling pathway that results in reduced translation. To directly test the role of mTOR signaling - and the role of 4E-BP activity in particular - in sleep deprivation-induced impairments, we will use a viral-expression approach in Specific Aim 1 to determine if expressing wild-type 4E-BP in the hippocampus is sufficient to restore memory and plasticity deficits induced by sleep deprivation. This approach will allow for carefully timed and cell type- and brain region-specific expression of 4E-BP with sleep deprivation. Finally, in Specific Aim 2 we will use a viral approach to determine if expressing phosphorylation-defective 4E-BP in the hippocampus will mimic the effects of sleep deprivation. Importantly, these experiments will allow us to determine if mTOR signaling plays a functional role in the memory and plasticity deficits observed with sleep loss.
描述(由申请人提供):睡眠丧失导致海马突触可塑性和海马依赖性记忆储存缺陷。然而,睡眠剥夺的这些影响背后的分子和细胞机制仍不清楚。一些研究表明,蛋白质合成途径在睡眠期间和睡眠剥夺后会发生改变。然而,以前没有人详细描述过睡眠或睡眠剥夺如何改变蛋白质合成,也没有人描述过这些改变如何调节记忆的形成。本研究旨在探讨哺乳动物雷帕霉素靶蛋白(mTOR)信号通路在睡眠和睡眠介导的记忆巩固过程中的蛋白质合成调控作用。这些实验将开发工具来分析大脑中的mTOR信号,并为mTOR信号在睡眠依赖性记忆巩固中的新作用提供直接证据。在本申请中,提出了两个具体目标,使用新的遗传方法来研究睡眠剥夺如何影响导致翻译减少的mTOR信号通路。为了直接测试mTOR信号传导的作用-特别是4 E-BP活性的作用-在睡眠剥夺诱导的损伤中,我们将在特定目标1中使用病毒表达方法来确定在海马中表达野生型4 E-BP是否足以恢复睡眠剥夺诱导的记忆和可塑性缺陷。这种方法将允许仔细定时和细胞类型和大脑区域特异性表达4 E-BP与睡眠剥夺。最后,在具体目标2中,我们将使用病毒方法来确定在海马中表达磷酸化缺陷的4 E-BP是否会模拟睡眠剥夺的影响。重要的是,这些实验将使我们能够确定mTOR信号传导是否在睡眠丧失时观察到的记忆和可塑性缺陷中发挥功能作用。
项目成果
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Jennifer Choi Tudor其他文献
Jennifer Choi Tudor的其他文献
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{{ truncateString('Jennifer Choi Tudor', 18)}}的其他基金
The role of mTOR signaling in the cognitive impact of sleep deprivation
mTOR 信号传导在睡眠剥夺认知影响中的作用
- 批准号:
8829701 - 财政年份:2014
- 资助金额:
$ 5.78万 - 项目类别:
APP Metabolism in Transgenic Down Syndrome Mouse Models
转基因唐氏综合症小鼠模型中的 APP 代谢
- 批准号:
7328761 - 财政年份:2007
- 资助金额:
$ 5.78万 - 项目类别:
APP Metabolism in Transgenic Down Syndrome Mouse Models
转基因唐氏综合症小鼠模型中的 APP 代谢
- 批准号:
7480918 - 财政年份:2007
- 资助金额:
$ 5.78万 - 项目类别:
APP Metabolism in Transgenic Down Syndrome Mouse Models
转基因唐氏综合症小鼠模型中的 APP 代谢
- 批准号:
7624245 - 财政年份:2007
- 资助金额:
$ 5.78万 - 项目类别: