Neurobiology of aging in the bat

蝙蝠衰老的神经生物学

• 批准号: 10527777
• 负责人: Rena Orman
• 金额: $ 16.15万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10527777
• 关键词: 1 year old; 10 year old; 5 year old; Address; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Animal Model; Basal Ganglia; Biological Assay; Biological Models; Birth; Brain; Brain region; Buffers; Calcium; Calcium-Binding Proteins; Calpain; Cells; Chiroptera; Claustral structure; DNA Methylation; Data; Disease; Disinhibition; Equilibrium; Excision; Family; Foundations; Fruit; Generations; Goals; Grant; Hippocampal Formation; Immunohistochemistry; Impairment; Individual; Interneurons; Lead; Link; Longevity; Modeling; Mus; Nerve Degeneration; Neuroanatomy; Neurobiology; Neurodegenerative Disorders; Neurons; Parkinson Disease; Parvalbumins; Pattern; Peptide Hydrolases; Physiologic pulse; Physiology; Pilot Projects; Primates; Proteins; Regulation; Rodent; Sampling; Slice; Structure; Tail; Testing; Tissues; Western Blotting; age group; age related; aging brain; brain dysfunction; calbindin; calretinin; cell type; human model; inhibitory neuron; insight; m-calpain; member; mu-calpain; multi-electrode arrays; neuron loss; normal aging; protein expression; regional difference; sensor; targeted treatment

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