Mechanistic Studies on the Impact of Sleep Deprivation on Gene Regulation
睡眠剥夺对基因调控影响的机制研究
基本信息
- 批准号:10286553
- 负责人:
- 金额:$ 34.47万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-01 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdultAffectAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAlzheimer&aposs disease related dementiaAlzheimer&aposs disease riskAmyloid beta-ProteinBilateralBrain regionCause of DeathCell NucleusCellsCessation of lifeChronicCognition DisordersDevelopmentDisease ProgressionDisease susceptibilityDorsalEconomic BurdenExhibitsFamilyFoundationsFutureGene ExpressionGene Expression RegulationGenesGenetic TranscriptionGenetic TranslationHealthHealthcareHippocampus (Brain)HumanImpaired cognitionIncidenceIndividualInjectionsInvestigationLabelLong-Term EffectsLongevityMedicalMemoryMessenger RNAMolecularMusMutateNeurodegenerative DisordersNeuronsNuclearNuclear RNAOnset of illnessPathogenesisPathologicPathologyPhenotypePolyribosomesPredispositionProcessProteinsPublic HealthRNARNA ProcessingRNA SplicingRNA-Binding ProteinsRegulationResearchResolutionRiboTagRibosomal ProteinsRibosomesRiskScienceSleepSleep DeprivationSleep disturbancesSocietiesSymptomsTauopathiesTechniquesTechnologyTeenagersTherapeuticTranslatingTranslationsUnited StatesViralWild Type Mousecare burdencell typedeprivationdisease phenotypeemerging adultexcitatory neuronexperimental studygenome-widegenome-wide analysisinsightmRNA ExpressionmRNA sequencingmouse modelnovelnovel therapeuticsparent grantpoor sleeprelating to nervous systemresponsesleep patterntau Proteinstau-1transcriptometranscriptome sequencingtranslatomeyoung adult
项目摘要
Project Summary/Abstract
Alzheimer's disease is now considered by some experts to be the third leading cause of death in the United
States, inflicting enormous health care and economic burdens on individuals, families and society. With
advances in medical science and technology substantially extending human lifespan, the numbers of
individuals living longer and affected by Alzheimer's disease and related dementias is expected to increase
significantly. While sleep disturbances have long been viewed as symptoms of Alzheimer's disease and other
neurodegenerative diseases, recent research has suggested that chronic sleep disruption may be a significant
risk factor for Alzheimer's disease decades later. Poor sleep patterns and chronic sleep loss also appear to
accelerate the rate of disease progression and pathogenesis. Acute and chronic sleep deprivation have also
been shown to increase tau pathologies and amyloid beta peptides, pathological hallmarks of Alzheimer's
disease. Recent estimates suggest that over 35% of adults suffer from chronic sleep deprivation making it
imperative that we identify the mechanisms through which chronic sleep deprivation affects Alzheimer's
pathogenesis. The hippocampus, a critical brain region for memory, is particularly susceptible to the effects of
sleep deprivation and is one of the first regions to exhibit phenotypic pathologies in Alzheimer's disease. We
hypothesize that chronic sleep deprivation causes aberrant nuclear RNA splicing and processing, and limits
the available pool of mRNA for translation to affect gene expression in tau pathogenesis. The objective of this
Alzheimer's disease Supplement proposal is to identify the impact of chronic sleep deprivation on
neuronal mRNA processing in the nucleus and to define the translatome of excitatory neurons in the
hippocampus in a mouse model of tauopathy related to Alzheimer's disease and related dementias. We
will use deep neuronal nuclear RNA sequencing to identify the impact of chronic sleep deprivation on mRNA
processing and splicing, and an advanced viral RiboTag strategy to specifically target excitatory neurons in the
hippocampus followed by deep RNA sequencing of the mRNA associated with translating polyribosomes in a
mouse model for tauopathies related to Alzheimer's disease. The results from our multi-level experiments
defining genome-wide impacts of chronic sleep deprivation with cell-type specific resolution on RNA
processing, and the identification of a cell-type specific translatome signature of chronic sleep deprivation, will
provide significant insights into the negative impacts of sleep deprivation on tau pathogenesis related to
Alzheimer's disease, potentially leading to the development of novel therapeutics to counteract the
consequences of sleep loss on cognition and neurodegenerative disorders.
项目总结/文摘
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)
专利数量(0)
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EDWIN TED G. ABEL其他文献
EDWIN TED G. ABEL的其他文献
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{{ truncateString('EDWIN TED G. ABEL', 18)}}的其他基金
University of Iowa Hawkeye Intellectual and Developmental Disabilities Research Center (Hawk-IDDRC)
爱荷华大学鹰眼智力与发育障碍研究中心 (Hawk-IDDRC)
- 批准号:
10451564 - 财政年份:2021
- 资助金额:
$ 34.47万 - 项目类别:
University of Iowa Hawkeye Intellectual and Developmental Disabilities Research Center (Hawk-IDDRC)
爱荷华大学鹰眼智力与发育障碍研究中心 (Hawk-IDDRC)
- 批准号:
10238630 - 财政年份:2021
- 资助金额:
$ 34.47万 - 项目类别:
University of Iowa Hawkeye Intellectual and Developmental Disabilities Research Center (Hawk-IDDRC)
爱荷华大学鹰眼智力与发育障碍研究中心 (Hawk-IDDRC)
- 批准号:
10669135 - 财政年份:2021
- 资助金额:
$ 34.47万 - 项目类别:
Mechanistic Studies on the Impact of Sleep Deprivation on Gene Regulation
睡眠剥夺对基因调控影响的机制研究
- 批准号:
10612844 - 财政年份:2019
- 资助金额:
$ 34.47万 - 项目类别:
Mechanistic Studies on the Impact of Sleep Deprivation on Gene Regulation
睡眠剥夺对基因调控影响的机制研究
- 批准号:
9980258 - 财政年份:2019
- 资助金额:
$ 34.47万 - 项目类别:
Mechanistic Studies on the Impact of Sleep Deprivation on Gene Regulation
睡眠剥夺对基因调控影响的机制研究
- 批准号:
10398122 - 财政年份:2019
- 资助金额:
$ 34.47万 - 项目类别:
Molecular, Cellular and Circuit Effects of Sleep Deprivation on Hippocampal Function
睡眠剥夺对海马功能的分子、细胞和回路影响
- 批准号:
10431989 - 财政年份:2018
- 资助金额:
$ 34.47万 - 项目类别:
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