The effect of cortisol on tooth development

皮质醇对牙齿发育的影响

• 批准号: 10908255
• 负责人: Christine Ida Shaffer
• 金额: $ 5.34万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-03 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10908255
• 关键词: Adolescent; Affect; Ameloblasts; Anxiety; Behavior Disorders; Biological Markers; Biosensor; Brain; Cell physiology; Cells; Child; Child Development; Cognitive; Computer software; Data; Data Set; Dental; Dental Enamel; Dentists; Development; Diagnosis; Early Intervention; Environment; Exposure to; Fetal Development; Foundations; Future; Glucocorticoids; Hormones; Human; Hydrocortisone; Image; Image Analysis; Immunohistochemistry; Impairment; Incisor; Individual; Life; Life Cycle Stages; Link; Major Depressive Disorder; Mandible; Measurable; Measurement; Measures; Mediating; Mental Health; Mental disorders; Mentors; Modernization; Morphology; Mus; Oral health; Output; Phenotype; Physiology; Pregnancy; Problem behavior; Production; Productivity; Proliferating; Publishing; Records; Reporting; Research; Research Personnel; Risk; Saline; Salivary; Signal Pathway; Signal Transduction; Source; Stress; Structure; Techniques; Testing; Thick; Thinness; Three-Dimensional Image; Time; Tooth Cell; Tooth Demineralization; Tooth structure; Variant; Work; World Health Organization; X-Ray Computed Tomography; clinical training; deciduous tooth; density; environmental stressor; experience; fetal; high risk; human data; in utero; kindergarten; microCT; mineralization; mouse model; peer; postnatal; pregnant; prenatal; prenatal exposure; prospective; pup; screening; skills; teeth clenching

PROJECT SUMMARY / ABSTRACT During pregnancy, excess levels of the glucocorticoid stress hormone, cortisol, is known to significantly alter fetal brain networks and result in long-term cognitive and behavioral problems. As of 2019, the World Health Organization recognizes 10-20% of children and adolescents experience mental health disorders worldwide. Without proper diagnosis and treatment, these conditions dramatically impact the child’s development and impairs their potential to live a productive life. A significant advance for the field would be the discovery of a biosensor that produces biomarkers of prenatal cortisol exposure, which may aid in the prospective identification of individuals with a higher risk of mental health disorders. Coincidentally, fetal ameloblasts in primary teeth lay down and mineralize the enamel matrix during the same developmental window in which critical fetal brain networks are established during gestation, making ameloblasts attractive candidates for biosensors. Once the enamel matrix is produced, it remains a stable structure for the duration of development, eruption, and after shedding of the primary tooth, making the primary tooth matrix a promising source of biomarkers. In support of this possibility, our lab previously found that primary teeth collected from kindergarten children with high salivary cortisol reactivity have reduced tooth enamel thickness and density. Cortisol reactivity in children is associated with increased levels of prenatal cortisol. In this proposal, I aim to determine a panel of tooth matrix biomarkers related to elevated prenatal cortisol exposure, and to identify the mechanisms by which ameloblasts are natural biosensors of alterations in the prenatal environment. Therefore, I will test my central hypothesis that teeth store permanent, measurable records of cortisol exposure as a result of altered ameloblast proliferation and maturation during tooth formation. I will use the following specific aims for these studies. Aim 1: Determine a panel of physical tooth measurements associated with increased cortisol reactivity. Aim 2: Identify the cellular mechanisms by which cortisol affects tooth morphology and enamel mineralization. These proposed studies will allow me to identify tooth matrix biomarkers that, collectively, produce a signature for increased prenatal cortisol exposure. In addition, results from this study will provide the foundation for future studies to investigate how ameloblasts can biologically detect and record other prenatal environmental stressors known to impact fetal development. This proposed research plan, combined with my dental clinical training, will provide me with the skills and experience I need to become an independent investigator.

项目概要/摘要 在怀孕期间，糖皮质激素应激激素皮质醇的过量水平已知会显着改变 胎儿大脑网络并导致长期的认知和行为问题。截至 2019 年，世界卫生组织 该组织承认全球 10-20% 的儿童和青少年患有精神健康障碍。 如果没有适当的诊断和治疗，这些情况会极大地影响儿童的发育和 削弱了他们过上富有成效的生活的潜力。该领域的一个重大进步是发现 产生产前皮质醇暴露生物标志物的生物传感器，这可能有助于前瞻性识别 患有精神健康障碍的风险较高的个人。巧合的是，胎儿的成釉细胞位于乳牙中 在关键胎儿大脑的同一发育窗口期间，使牙釉质基质下降并矿化 网络在妊娠期间建立，使成釉细胞成为生物传感器的有吸引力的候选者。一旦 牙釉质基质产生后，在发育、萌出和之后的整个过程中都保持稳定的结构 乳牙脱落，使乳牙基质成为生物标志物的有前途的来源。支持 这种可能性，我们实验室之前发现，从幼儿园儿童采集的乳牙唾液量高 皮质醇反应性降低了牙釉质厚度和密度。儿童皮质醇反应性与 产前皮质醇水平增加。在本提案中，我的目标是确定一组牙基质生物标志物 与产前皮质醇暴露升高有关，并确定成釉细胞天然的机制 产前环境变化的生物传感器。因此，我将检验我的中心假设：牙齿 存储由于成釉细胞增殖改变而导致的皮质醇暴露的永久、可测量的记录 牙齿形成过程中的成熟。我将使用以下具体目标进行这些研究。目标 1：确定 一组与皮质醇反应性增加相关的物理牙齿测量值。目标 2：识别细胞 皮质醇影响牙齿形态和牙釉质矿化的机制。 这些拟议的研究将使我能够识别牙基质生物标志物，这些生物标志物共同产生一个特征 增加产前皮质醇暴露。此外，本研究的结果将为未来的研究奠定基础 研究成釉细胞如何从生物学角度检测和记录其他产前环境压力源 已知会影响胎儿发育。这项拟议的研究计划与我的牙科临床培训相结合，将 为我提供成为独立调查员所需的技能和经验。