Metabolomic characterization of normal aging and Alzheimer's disease under anesthesia- surgery stimuli

麻醉手术刺激下正常衰老和阿尔茨海默病的代谢组学特征

• 批准号: 10350570
• 负责人: Leo L Cheng
• 金额: $ 78.67万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-15 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10350570
• 关键词: AD transgenic mice; Aftercare; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease patient; Anesthesia procedures; Animal Behavior; Animal Model; Animals; Anti-Inflammatory Agents; Blood; Brain; Brain region; Clinic; Clinical; Clinical Protocols; Cyclosporine; Development; Diffusion Magnetic Resonance Imaging; Electron Microscope; Evaluation; Foundations; Functional Magnetic Resonance Imaging; Gluconeogenesis; Glucose; Goals; Homeostasis; Hour; Human; Image; Immunochemistry; Impairment; Individual; Intervention; Knock-out; Label; Lead; Longevity; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Metabolic; Methods; Mitochondria; Monitor; Mus; Onset of illness; Operative Surgical Procedures; Organ; Pathogenesis; Pathway interactions; Patients; Predisposition; Preventive; Procedures; Protocols documentation; Rest; Serum; Stimulus; Technology; Testing; Time; Tissue Harvesting; Tissues; Training; Transgenic Organisms; Translating; Validation; Vitamin K 2; Wild Type Mouse; arm; base; behavior test; brain tissue; cohort; design; in vivo; in vivo imaging; in vivo magnetic resonance spectroscopy; metabolomics; mitochondrial dysfunction; morris water maze; mouse model; multimodality; myelination; neuroinflammation; noninvasive diagnosis; normal aging; novel; success; tool

We propose to quantify aging- and AD-associated brain and blood metabolic changes through ex vivo and in vivo multimodality MR measurements in mouse models after an AD-promoting stimuli, anesthesia-surgery, with-or-without preventive, protective treatments. This approach recognizes that AD onset, pathogenesis and progression must produce alterations in the overall metabolic status, or metabolomics, of brain and other organs in AD patients, as compared with normal homeostasis in healthy individuals, and our understanding of the urgent need to develop non-invasive AD diagnosis tools. In the three proposed Aims, we will (1) Characterize age-associated metabolomic changes ex vivo using tissues from different brain regions and blood serum obtained from wild-type and AD mice after administration of anesthesia-surgery stimuli; (2) Develop multimodality in vivo MR protocols for non-invasive evaluations of age- and AD-associated brain metabolic changes induced by anesthesia-surgery stimuli; and (3) Investigate the effect of an AD protective intervention on metabolomic changes after administration of anesthesia-surgery stimuli. The success of this project will lead us to establish translational protocols that can guide and interpret multimodality in vivo MR imaging results by obtaining accurate ex vivo MRS, EM, and immunochemistry measurements in the proposed animal models, and translating these findings into clinical protocols for human AD non-invasive diagnosis.

我们建议通过离体和体内量化衰老和ad相关的脑和血液代谢变化