The neural basis for aging-dependent decline in taste function
The neural basis for aging-dependent decline in taste function
批准号:
10191207
负责人:
Elizabeth Brown
金额:
$10.0万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-09-01 至 2023-08-31
关键词:
AffectAfferent NeuronsAgeAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAmyloid beta-42Amyloid beta-ProteinBehavioralBrain regionCellsCyclic AMPDataDetectionDrosophila genusDrosophila melanogasterFunctional ImagingFunctional disorderGTP-Binding Protein alpha Subunits, GsGenesGeneticGenomic approachHumanImageImpairmentInvestigationLibrariesMeasuresMediatingMemoryMemory impairmentMentorsModelingMolecularMushroom BodiesNerve DegenerationNeurodegenerative DisordersNeuronal DysfunctionNeuronsNeurophysiology - biologic functionPathologyPathway interactionsPhasePhenocopyPhysiologicalPhysiologyProcessProtein IsoformsRNA InterferenceRNA interference screenSensorySignal PathwaySignal TransductionStructureStudy modelsSynapsesTaste PerceptionTauopathiesTestingToxic effectTrainingTransgenesVariantage effectage relatedagedcell typeexperimental studyflygenetic manipulationgenome-widehealthy agingin vivoinsightknock-downnormal agingnovelpathological agingrelating to nervous systemresponsescreeningsensorsugartaste systemtau Proteinstranscriptome sequencing
中文摘要
项目总结
化学感觉处理的缺陷与健康的衰老以及许多神经退行性变有关。
包括阿尔茨海默病(AD)在内的各种疾病。在许多情况下,化学感觉缺陷预示着
神经退行性疾病,并了解这些变化的机制基础可能有助于洞察
与衰老和神经退化相关的基本功能障碍。遗传学和生理学
化学感觉神经元及其定义的更高阶处理中心的可及性提供了独特的
研究与衰老相关的过程对神经功能,包括感觉的影响的机会
反应性、可塑性和突触连通性。果蝇,黑腹果蝇,是一个强大的模型
用于研究化学感觉、衰老和衰老相关的病理,但衰老对化学感觉的影响
在这种模式下仍然很大程度上没有被探索,特别是在品味方面。一个大型遗传工具包,结合了
功能成像允许对味觉回路进行细胞类型的特定操作。AD BE的多种型号
在果蝇中发生,主要表现为AD的两个特征:淀粉样β蛋白(Aβ)介导的毒性和
由于Tau蛋白过度磷酸化而引起的肌萎缩侧索硬化。我的初步研究结果显示,
知觉和味觉记忆随着年龄的增长而恶化,这在阿尔茨海默病的苍蝇模型中加剧。在这里,我会
研究增龄相关味觉和味觉记忆减退的生理和分子基础
自然衰老和病理性衰老。这些实验建立在我在化学传感处理方面的专业知识和
功能成像,同时提供衰老和基因组方法方面的培训。
英文摘要
PROJECT SUMMARY
Deficits in chemosensory processing are associated with healthy aging, as well as numerous neurodegenerative
disorders including Alzheimer’s Disease (AD). In many cases, chemosensory deficits are harbingers of
neurodegenerative disease, and understanding the mechanistic basis for these changes may provide insight into
fundamental dysfunction associated with aging and neurodegeneration. The genetic and physiological
accessibility of chemosensory neurons and their defined higher order processing centers provide a unique
opportunity to investigate the effects of aging-related processes on neural function, including sensory
responsiveness, plasticity, and synaptic connectivity. The fruit fly, Drosophila melanogaster, is a powerful model
for studying chemosensation, aging, and aging-related pathologies, yet the effects of aging on chemosensation
remain largely unexplored in this model, particularly with respect to taste. A large genetic toolkit combined with
functional imaging allow for cell-type specific manipulation of taste circuits. Numerous models of AD been
developed in Drosophila that largely phenocopy two hallmarks of AD: amyloid beta (Aβ)-mediated toxicity and
tauopathy caused by hyperphosphorylation of the Tau protein. My preliminary findings reveal that taste
perception and taste memory deteriorate with age, and this is exacerbated in a fly model of AD. Here, I will
examine the physiological and molecular basis for age-associated reduction in taste and taste memory in models
of natural and pathological aging. These experiments build on my expertise in chemosensory processing and
functional imaging, while providing training in aging and genomic approaches.
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The neural basis for aging-dependent decline in taste function
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批准号:10558556
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项目类别:
-
资助金额:$10.0万
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财政年份:2021
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负责人:Elizabeth Brown
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依托单位:
海外基金