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Mitochondrial, antioxidant and cognitive effects of Centella asiatica during aging

积雪草在衰老过程中的线粒体、抗氧化和认知作用

基本信息

批准号：
9762849
负责人：
Nora Gray
金额：
$ 23.48万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9762849
关键词：
Acids Acute Address Age-Months Age-associated memory impairment Aging Alternative Therapies Alzheimer&apos s Disease Alzheimer&apos s disease model Amyloid beta-Protein Antioxidants Attenuated Award Ayurvedic Medicine Basic Science Behavior assessment Behavioral Biochemical Pathway Bioenergetics Biogenesis Biological Models Botanicals Brain Cell Culture Techniques Cell Death Cell Line Chronic Clinical Trials Cognition Cognitive Communication Complementary and alternative medicine Data Development Development Plans Diet Dietary Intervention Elements Evaluation Exposure to Future Gene Expression Genes Goals Gotu kola Grant Health Health Sciences Herb Human Impaired cognition Impairment In Vitro Individual Knock-out Knowledge Leadership Learning Long-Term Effects Mainstreaming Medicinal Plants Memory Mentors Mentorship Methods Mitochondria Molecular Monitor Morphology Mus Neurobiology Neurodegenerative Disorders Neurologic Neurons Oral Administration Oregon Oxidative Stress Pathway interactions Phase Physiological Plants Play Reporting Research Research Personnel Research Technics Rodent Model Role Senile Plaques Slice Techniques Testing Tg2576 Therapeutic Therapeutic Agents Therapeutic Intervention Training Translational Research Triterpenes Universities Water Work Writing abeta accumulation abeta toxicity aged attenuation behavior test career career development cognitive enhancement cognitive function cohort executive function experimental study healthy aging improved in vitro Model in vivo in vivo Model inhibitor/antagonist insight interest mitochondrial dysfunction neuroblastoma cell neuron loss neurotoxicity new therapeutic target overexpression oxidative damage prevent public health relevance research and development response skills skills training success transcription factor

项目摘要

DESCRIPTION (provided by applicant): This proposal outlines a research and career development plan that builds on Dr. Gray's existing training and allows her to: 1) gain expertise with in vitro and in vivo methods to study the neurobiology of cognitive impairment; 2) acquire detailed knowledge of techniques and advances in mitochondrial research; 3) solidify skills to characterize botanical products and perform rigorous complementary and alternative medicine research; and 4) build and strengthen the skills needed for success as an independent investigator. Dr. Gray's superb mentorship and collaborative training team are all located at Oregon Health and Science University (OHSU) making it an ideal setting for the K99 phase of this award. In addition to providing world-class training in basic and translational research techniques, numerous courses and seminars are available at OHSU to strengthen the communication, leadership and grant writing capabilities essential for achieving her long-term career goal of conducting independent research on neurologically active botanical and dietary interventions. The goal of the proposed research is to determine how the medicinal plant Centella asiatica (L.) Urban (CA) modulates mitochondrial function and antioxidant response to elicit its neuroprotective and cognitive- enhancing effects. CA is an Ayurvedic herb used to improve cognitive function, an effect supported by studies in humans and numerous rodent models. Our lab has shown that CA water extract (CAW) can improve learning and memory in aged wild-type as well as Tg2576 mice, an Alzheimer's Disease (AD) model of beta- amyloid (Aß) accumulation, and protect neuroblastoma cells against Aß-induced cell death. Our preliminary in vitro and in vivo data show that CAW activates the endogenous antioxidant response pathway and induces mitochondrial biogenesis. This proposal will determine how each of those pathways contributes to the neuroprotective and cognitive-enhancing effects of CAW. In Aim 1 Dr. Gray will be trained in and apply the more physiologically relevant in vitro model system of primary neuronal cell culture to determine the molecular mechanism by which CAW protects against Aß toxicity. In Aim 2, a battery of behavioral assessments will be learned and used to determine which aspects of cognition are altered by CAW, and how its antioxidant and mitochondrial effects contribute to these cognitive-enhancing effects. Aim 2 will also explore the preventative potential of CAW by assessing the cognitive effects and underlying mechanisms of long-term CAW treatment. This work will address critical gaps in our understanding of the mechanism of CAW and how mitochondrial and antioxidant pathways interact and participate in modulating neuronal health and cognition using powerful in vitro and in vivo models of AD. The results and techniques established here will help identify specific targets for future therapeutic intervention with botanical or dietary agents in the context of AD a well as other conditions with cognitive impairment and will lead to better-informed clinical trials of such treatments. The skills and training provided by the K99 award will launch Dr. Gray's active, independent research career.