Neurobiology of aging in the bat
蝙蝠衰老的神经生物学
基本信息
- 批准号:10527777
- 负责人:
- 金额:$ 16.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:1 year old10 year old5 year oldAddressAffectAgeAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAnimal ModelBasal GangliaBiological AssayBiological ModelsBirthBrainBrain regionBuffersCalciumCalcium-Binding ProteinsCalpainCellsChiropteraClaustral structureDNA MethylationDataDiseaseDisinhibitionEquilibriumExcisionFamilyFoundationsFruitGenerationsGoalsGrantHippocampal FormationImmunohistochemistryImpairmentIndividualInterneuronsLeadLinkLongevityModelingMusNerve DegenerationNeuroanatomyNeurobiologyNeurodegenerative DisordersNeuronsParkinson DiseaseParvalbuminsPatternPeptide HydrolasesPhysiologic pulsePhysiologyPilot ProjectsPrimatesProteinsRegulationRodentSamplingSliceStructureTailTestingTissuesWestern Blottingage groupage relatedaging brainbrain dysfunctioncalbindincalretinincell typehuman modelinhibitory neuroninsightm-calpainmembermu-calpainmulti-electrode arraysneuron lossnormal agingprotein expressionregional differencesensortargeted treatment
项目摘要
ABSTRACT
Calcium dysregulation is a critical contributor to neuronal loss in normal aging and neurodegenerative
diseases. An important cause of calcium dysregulation is the loss of calcium binding proteins such as
parvalbumin, calbindin and calretinin. They serve as calcium buffers/sensors in many cells, especially
inhibitory neurons. An important consequence of calcium dysregulation is calpain activation, which is
postulated to cause brain aging and neurodegeneration. We hypothesize that there is (1) a progressive loss
of inhibitory neurons expressing calcium binding proteins, (2) disinhibition in affected brain regions, and (3)
increased calpain activation due to disinhibition as a function of age. Calpain activity will thus drive
neurodegeneration due to aging. To address this, we propose to use an attractive, but understudied model
of aging: Carollia perspicillata, the short-tailed fruit bat. Carollia has a lifespan >10 years and their
neuroanatomy is closer to that of primates than rodents are. We will determine age-dependent changes in
claustrum, hippocampal formation, and basal ganglia. Specifically, we will evaluate the expression of
calcium binding proteins (parvalbumin, calbindin, calretinin) and the expression and activity of calpains 1
and 2 and relate these changes to inhibitory control of neuronal networks. The data obtained from this pilot
grant will serve as a foundation for detailed mechanistic studies of neurodegeneration caused by aging and
disease.
摘要
项目成果
期刊论文数量(0)
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Rena Orman其他文献
Rena Orman的其他文献
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