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IGF-1 Regulation of Astrocyte Mitochondrial Metabolism and Redox Homeostasis in Brain Aging

IGF-1 对星形胶质细胞线粒体代谢和脑衰老过程中氧化还原稳态的调节

基本信息

批准号：
9788204
负责人：
Sreemathi Logan
金额：
$ 12.42万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9788204
关键词：
Address Age Age-associated memory impairment Aging Animals Antioxidants Applications Grants Area Astrocytes Behavior assessment Bioenergetics Blood Vessels Brain Cells Charge Chronic Cognition Cognitive Cognitive Therapy Cognitive deficits Collaborations Data Disease Electron Transport Energy Metabolism Ensure Faculty Functional disorder Funding Gene Expression Genus Hippocampus Glial Fibrillary Acidic Protein Goals Growth Factor Health Hippocampus (Brain)Homeostasis Human Impaired cognition Impairment In Vitro Incidence Individual Injections Journals Knock-out Knockout Mice Knowledge Laboratories Learning Long-Term Potentiation MAPK8 gene Maintenance Malignant Neoplasms Measurement Memory Memory impairment Mentors Metabolic Mitochondria Modeling Molecular Mus NF-kappa B Neurodegenerative Disorders Neurons Neurosecretory Systems Oklahoma Oxidation-Reduction Oxidative Regulation Oxidative Stress Oxygen Consumption Pathway interactions Pharmacology Production Quality of life Reactive Oxygen Species Regulation Reporting Research Research Activity Research Personnel Risk Role Scientist Secure Series Shock Signal Pathway Signal Transduction Somatomedins Stress Techniques Testing Therapeutic Intervention Time Tissues Training Training Programs Traumatic Brain Injury age related age related neurodegeneration aged aging brain authority brain health brain tissue cell type cognitive function cognitive reappraisal experimental study gain of function improved in vivo insulin signaling knock-down laboratory experience loss of function member metabolomics mitochondrial metabolism neuron loss novel overexpression oxidative damage prevent programs response targeted treatment therapeutic target

项目摘要

PROJECT SUMMARY/ABSTRACT The long-term goal of this project is to establish Dr. Logan as a successful and funded, independent investigator in the field of aging, and in particular, mitochondrial redox homeostasis and brain aging. Dr. Logan joined the laboratory of Dr. William Sonntag to study the mechanisms underlying IGF-1-dependent changes in learning and memory. Dr. Sonntag is a leading authority in the field of neuroendocrine signaling and aging. Dr. Sonntag's laboratory offers a variety of in vivo approaches, which will expand her technical repertoire and allow her to become a well-rounded research scientist. The research strategy outlined incorporates in vitro techniques used to study mitochondrial metabolism with the in vivo techniques in the Sonntag laboratory. The training program includes a mixture of hands-on laboratory training, journal clubs and mentoring interactions with Dr. Van Remmen and members of the Oklahoma Nathan Shock Center. Dr. Logan will receive specialized training in mitochondrial function and signaling networks directly relevant to this area of research. This program will ensure that Dr. Logan transitions to an independent investigator in the field of aging research. The short-term objective of this application is to enhance the candidate's knowledge of mitochondrial metabolism and redox homeostasis and long-term to enable the candidate, as a newly-hired faculty member, to secure protected time for research activity, establish new collaborations, and pursue a novel line of independent research that results in competitive grant proposals. Preliminary data performed by Dr. Logan indicate that IGF-1 regulates energy levels in astrocytes rather than neurons; loss of IGF-1 signaling reduces energy charge in astrocytes, increases mitochondrial ROS that when chronically sustained leads to learning and memory impairments. This proposal expands these novel findings to better understand how IGF-1-regulated mitochondrial bioenergetics and redox signaling contribute to age-related cognitive decline. The overarching hypothesis is that aberrations in astrocytic redox and energy homeostasis contribute to cognitive deficits with age. The following aims are proposed: 1) Determine whether IGF-1R signaling deficiency impairs astrocyte mitochondrial function and bioenergetics; 2) Decipher the molecular regulation of redox homeostasis in astrocytes with IGF-1R signaling deficiency; and 3) Delineate the functional consequence of IGF-1R signaling in astrocytes on learning and memory. The studies that have been proposed will explore pathways that increase the risk for neurodegenerative disease, contribute to cognitive impairment and potentially be targeted to improve the quality of life for older individuals.

项目总结/文摘