Defining the Targets and Function of Direct Trigeminal Sensory Innervation to Salivary Glands

定义唾液腺直接三叉神经感觉神经支配的目标和功能

基本信息

批准号：
10558821
负责人：
Isabelle M.A. Lombaert
金额：
$ 64.32万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-13 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10558821
关键词：
Afferent Neurons Anatomy Animal Model Antihypertensive Agents Anxiety Atrophic Attention Autoimmune Diseases Autonomic nervous system Bioinformatics Brain Cancer Etiology Cannulations Cells Chemotherapy and/or radiation Classification Comparative Anatomy Deglutition Dental caries Duct (organ) structure Esthesia Etiology Evaluation Excision Family suidae Feedback Fiber Fluorescence-Activated Cell Sorting Functional Imaging Functional disorder Gland Glandular Cell Goals Health Human Immunofluorescence Immunologic Impairment In Situ Individual Infusion procedures Insufflation Label Ligation Liquid substance Mammals Maps Mastication Mediating Miniature Swine Molecular Monitor Morbidity - disease rate Mucous Membrane Mus Nervous System Nervous System control Neurons Obstruction Operative Surgical Procedures Oral Oral health Organ Output Pain Parasympathetic Nervous System Parotid Gland Pathway interactions Patients Pattern Peripheral Pharmaceutical Preparations Population Production Proteins Reporter Reporting Research Rodent Role Saliva Salivary Salivary Glands Sensory Sialolithiasis Sjogren&apos s Syndrome Smell Perception Stensen&apos s duct Stimulus Structure Structure of mucous membrane of nose Sympathetic Nervous System Taste Perception Thick Tissues Tongue Trigeminal System Viral Viscosity Visualization Work Xerostomia adeno-associated viral vector appetite loss autoimmune pathogenesis calcium indicator cancer therapy cell type craniofacial tissue experience global health in vivo insight intercellular communication irritation nerve supply neuron component novel novel therapeutic intervention optogenetics oral pain orofacial regenerative therapy response saliva mediated saliva secretion single-cell RNA sequencing somatosensory spatiotemporal stressor tool transcriptomics

项目摘要

PROJECT SUMMARY: Saliva is essential for oral and global health. The indispensable oral fluid - produced by salivary glands - facilitates chewing, swallowing, speaking, and gustation. Loss of saliva (i.e. dry mouth) represents a significant health burden, and can be caused by cancer treatments, medications (e.g. anti-hypertensives), or autoimmune destruction of the gland. Patients report significant suffering when they lose saliva because they begin to experience life-long morbidities, such as alterations in taste, loss of appetite, mucosal irritation and oral pain. To date, additional treatments and therapies are needed to stimulate saliva production to alleviate dry mouth. The autonomic nervous system is the primary controller of saliva production and release. However, the brain and other neuronal components provide input to stimulate or inhibit these salivary autonomic neurons. Here, we investigate a novel aspect of the nervous system that may influence salivary gland function: the trigeminal somatosensory neurons that innervate the glands. We hypothesize that somatosensory neurons innervating the gland respond to local stressors and influence saliva production. The overall objective of this application is to use both small and large animal models to a) examine the glandular cell targets of the trigeminal sensory innervation, b) define the molecular identity of gland-innervating sensory neurons, c) characterize the stimuli that activate sensory neurons, and d) determine how sensory innervation influences saliva production. We will use an array of powerful, cutting-edge approaches to develop a comprehensive view of these enigmatic neurons across mammalian species. Our studies will reveal new information on the topographical and molecular mapping of sensory innervation in the gland, and the functional involvement of sensory neurons in saliva production. Ultimately, new therapeutic strategies will develop from this work that target increasing saliva production in patients suffering from dry mouth.

项目摘要：唾液对于口服和全球健康至关重要。不可或缺的口服液 - 由唾液腺产生 - 促进咀嚼，吞咽，说话和阵风。唾液损失（即干口解）代表着重要的健康状况负担，可能是由癌症治疗，药物（例如抗渗透剂）或自身免疫性引起的破坏腺体。患者失去唾液时会遭受重大痛苦，因为他们开始经历终生的病态，例如味觉改变，食欲不振，粘膜刺激和口腔疼痛。到日期，需要其他疗法和疗法来刺激唾液产生以减轻口干。自主神经系统是唾液产生和释放的主要控制器。但是，大脑和其他神经元成分提供了刺激或抑制这些唾液自主神经元的输入。在这里，我们研究神经系统的新方面，可能影响唾液腺功能：三叉神经支配腺体的体感神经元。我们假设体感神经元支配了腺对局部压力响应并影响唾液产生。该应用程序的总体目的是使用小动物模型和大型动物模型a）检查三叉神经感觉的腺细胞靶神经，b）定义腺体引起的感觉神经元的分子身份，c）表征刺激激活感觉神经元，d）确定感觉神经如何影响唾液产生。我们将使用一系列强大的，尖端的方法，以发展这些神经元的全面观点跨哺乳动物。我们的研究将揭示有关感觉神经的地形和分子图的新信息腺体以及感觉神经元在唾液产生中的功能参与。最终，新的治疗性这项工作将制定策略，以增加口腔干性患者的唾液产量增加。