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

• 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
• 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' s Syndrome; Smell Perception; Stensen' 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

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.

项目概要： 唾液对口腔和全球健康至关重要。唾液腺分泌的不可或缺的口腔液体 咀嚼、吞咽、说话和品尝。唾液流失（即口干）代表了一个重要的健康问题， 负担，并且可以由癌症治疗、药物（例如抗高血压药）或自身免疫性疾病引起。 腺的破坏。患者报告说，当他们失去唾液时，他们会感到非常痛苦，因为他们开始 经历终生的疾病，如味觉改变、食欲不振、粘膜刺激和口腔疼痛。到 因此，需要额外的治疗和疗法来刺激唾液产生以缓解口干。 自主神经系统是唾液产生和释放的主要控制器。然而，大脑 和其它神经元成分提供输入以刺激或抑制这些唾液自主神经元。这里我们 研究可能影响唾液腺功能的神经系统的新方面：三叉神经 支配腺体的躯体感觉神经元。我们假设支配大脑皮层的躯体感觉神经元 腺体对局部应激源作出反应并影响唾液产生。本申请的总体目标是 使用小型和大型动物模型来a）检查三叉神经感觉的腺细胞靶 神经支配，B）定义腺体支配感觉神经元的分子身份，c）表征 激活感觉神经元，和d）确定感觉神经支配如何影响唾液产生。我们将使用 一系列强大的尖端方法来全面了解这些神秘的神经元 在哺乳动物物种中。 我们的研究将揭示新的信息的地形和分子映射的感觉神经支配， 腺体，以及感觉神经元在唾液产生中的功能参与。最终，新的治疗方法 从这项工作中将开发出针对口干患者增加唾液产生的策略。