Psychobiological Regulation of Cell-Free Mitochondrial DNA in Human Saliva

人类唾液中游离线粒体 DNA 的心理生物学调节

• 批准号: 10455009
• 负责人: Martin Picard
• 金额: $ 12.15万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-22 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10455009
• 关键词: Acute; Adult; Affect; Age; Bacteria; Biological; Biological Markers; Blood; Blood Circulation; Body Fluids; Cells; Clinical; Collection; Corticosterone; Cortisone; Cost Measures; DNA; Data; Disease; Diurnal Rhythm; Ecological momentary assessment; Energy Metabolism; Estradiol; Exhibits; Feeling; Female; Foundations; Functional disorder; Future; Genome; Glucocorticoids; Health; Hormones; Hour; Human; Hydrocortisone; Inflammation; Inflammatory; Infrastructure; Laboratories; Link; Maps; Mass Spectrum Analysis; Measurable; Measures; Mediator of activation protein; Mental Health; Metabolic; Methods; Mitochondria; Mitochondrial DNA; Moods; Neuroimmune; Organelles; Outcome; Parents; Persons; Physical activity; Plasma; Positioning Attribute; Premenopause; Process; Progesterone; Protocols documentation; Psychological Stress; Psychopathology; Psychosocial Stress; Recovery; Regulation; Research; Rest; Role; Running; Saliva; Sex Differences; Signal Transduction; Stress; Testosterone; Time; Transducers; Trier Social Stress Test; Variant; Woman; Work; anxious; base; cohort; cost effective; design; epidemiology study; food consumption; immunogenic; men; negative affect; psychobiologic; response; saliva sample; steroid hormone; stress reactivity; systematic review; tool; volunteer; Acute; Adult; Affect; Age; Bacteria; Biological; Biological Markers; Blood; Blood Circulation; Body Fluids; Cells; Clinical; Collection; Corticosterone; Cortisone; Cost Measures; DNA; Data; Disease; Diurnal Rhythm; Ecological momentary assessment; Energy Metabolism; Estradiol; Exhibits; Feeling; Female; Foundations; Functional disorder; Future; Genome; Glucocorticoids; Health; Hormones; Hour; Human; Hydrocortisone; Inflammation; Inflammatory; Infrastructure; Laboratories; Link; Maps; Mass Spectrum Analysis; Measurable; Measures; Mediator of activation protein; Mental Health; Metabolic; Methods; Mitochondria; Mitochondrial DNA; Moods; Neuroimmune; Organelles; Outcome; Parents; Persons; Physical activity; Plasma; Positioning Attribute; Premenopause; Process; Progesterone; Protocols documentation; Psychological Stress; Psychopathology; Psychosocial Stress; Recovery; Regulation; Research; Rest; Role; Running; Saliva; Sex Differences; Signal Transduction; Stress; Testosterone; Time; Transducers; Trier Social Stress Test; Variant; Woman; Work; anxious; base; cohort; cost effective; design; epidemiology study; food consumption; immunogenic; men; negative affect; psychobiologic; response; saliva sample; steroid hormone; stress reactivity; systematic review; tool; volunteer

PROJECT SUMMARY Mitochondria are an emerging signaling organelle involved in stress regulation and mental health. Identifying mechanisms of mitochondrial signaling, including secreted molecules and their dynamic regulation, will provide the necessary tools to elucidate their role in stress pathophysiology and other disease conditions. We and others have recently established that mitochondria can release their own genome as cell-free mitochondrial DNA (cf- mtDNA), a potentially immunogenic molecule present in varying levels in human blood, particularly under conditions of psychological stress and psychopathology. Building on our recent discovery that cf-mtDNA is detectable in human saliva, we now propose foundational studies necessary to establish saliva cf-mtDNA as a useful marker for human research. Based on our preliminary studies, this 2-year R21 proposal aims to i) map the natural awakening response and diurnal variation of cf-mtDNA in healthy adult premenopausal women and in men; ii) define the association between cf-mtDNA and key steroid hormones with already well-defined diurnal rhythms, including cortisol; iii) leveraging already-collected saliva samples from a stress induction protocol, establish whether saliva cf-mtDNA is inducible by acute socioevaluative stress; and iv) whether saliva cf-mtDNA mirrors blood levels or whether cf-mtDNA is independently regulated in these two different biofluids. Together, these studies will establish potential sex differences in saliva cf-mtDNA dynamic across time scales, and provide the necessary basis to establish cf-mtDNA as a marker of mitochondrial stress in both mechanistic and epidemiological studies.

项目摘要 线粒体是参与压力调节和心理健康的新兴信号传导。识别 线粒体信号传导的机制，包括分泌分子及其动态调节，将提供 阐明其在压力病理生理学和其他疾病状况中的作用的必要工具。我们和其他人 最近确定线粒体可以释放自己的基因组作为无细胞的线粒体DNA（CF- mtDNA），一种潜在的免疫原性分子，在人类血液中存在不同的水平，尤其是在 心理压力和心理病理学的条件。基于我们最近发现CF-MTDNA是 在人类唾液中可检测的我们现在提出的基础研究是建立唾液CF-mtDNA作为一种 人类研究的有用标记。根据我们的初步研究，这项为期两年的R21提案旨在i）地图 健康成人绝经前妇女和 在男人ii）定义CF-MTDNA与关键类固醇激素与已经定义明确的昼夜的关联 节奏，包括皮质醇； iii）从应力诱导方案中利用已经收集的唾液样本， 确定唾液CF-MTDNA是否可以通过急性社会评估应力诱导； iv）是否唾液CF-MTDNA是否 反射血液水平，或者在这两种不同的生物流体中是否独立调节CF-MTDNA。一起， 这些研究将在跨时间范围内建立唾液CF-MTDNA动态的潜在性别差异，并提供 在机械和 流行病学研究。