Anatomical Specializations of the Human Pharynx

人类咽部的解剖学特点

• 批准号: 7596497
• 负责人: LIANCAI MU
• 金额: $ 27.39万
• 依托单位: HACKENSACK UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2009-09-17
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7596497
• 关键词: 3 year old; ATP phosphohydrolase; Acetylcholinesterase; Adult; Aging; Anatomy; Area; Articulators; Aspiration Pneumonia; Biochemical; Cardiac; Cause of Death; Communities; Condition; Data; Deglutition; Deglutition Disorders; Development; Dilator; Disease; Electrophoresis; Enzymes; Esophageal; Failure; Fiber; Functional disorder; Goals; Grant; Human; Immunoblotting; Internet; Knowledge; Larynx; Life; Macaca; Maintenance; Mammals; Metabolic; Methods; Monkeys; Motor; Motor Endplate; Movement; Muscle; Muscle Fibers; Myosin ATPase; Myosin Heavy Chains; Names; Nasopharynx; Nerve; Newborn Infant; Obstructive Sleep Apnea; Oropharyngeal; Palatal Muscles; Parkinson Disease; Pathogenesis; Pathologic; Pattern; Pharyngeal structure; Phenotype; Physiology; Play; Principal Investigator; Production; Property; Protein Isoforms; Research; Research Personnel; Respiration; Role; Shapes; Side; Silver Staining; Site; Sleep; Soft Palate; Specimen; Speech; Sphincter; Staining method; Stains; Structure; Sublingual Region; Surface; Systemic disease; Techniques; Testing; Tissues; Tongue; Upper Esophageal Sphincter; Work; age group; age related; airway obstruction; base; comparative; human very old age (85+); hypopharynx; immunocytochemistry; improved; interest; nerve supply; nervous system disorder; nonhuman primate; novel; pharynx muscle; size; soft tissue; vocal cord; vocalization

DESCRIPTION (provided by applicant): This renewal represents an expansion of the previous application with a new focus on exploring the anatomical and biochemical specializations of the pharyngeal dilator (genioglossus, GG), pharyngeal constrictors (PCs), upper esophageal sphincter (UES) and palatal muscles in: 1) 0-3 years old and 70-85 years old humans; 2) pathological human specimens with idiopathic Parkinson's disease (IPD); and 3) adult macaque monkey. The long-term goal of this application is to improve our understanding of the neuromuscular control of the upper airway functions and of the mechanisms causing dysphagia and obstructive sleep apnea in an effort to develop novel therapies for treating both life-threatening disorders. The pharyngeal muscles play vital roles in maintenance of upper airway patency and pharyngeal swallowing. Dysfunction of these muscles is related to the occurrence of upper airway disorders. However, the pathogenesis of these disorders remains poorly understood. Our preliminary studies showed that the adult human GG was divided into slow horizontal and fast oblique compartments. The PCs and UES were composed of a slow inner layer and a fast outer layer which were innervated by the IX and X nerves, respectively. It is interesting to note that the histochemically defined fiber layers in the PCs were obscured with aging. Another important finding was that the adult pharyngeal muscles contained muscle fibers expressing unusual myosin heavy chain (MHC) isoforms (slow-tonic and alpha-cardiac) which were concentrated predominantly in the slow horizontal GG and slow inner layer of the PCs. Based on these novel observations, we hypothesize that the adult human pharyngeal muscles have been specialized as a result of functional demands and that differences in the fiber type and MHC composition in the pharyngeal muscles exist between different age groups of normal humans, between normal adult human and IPD, and between human and non-human primates. The hypotheses will be tested with the following 2 specific aims. Specific Aim 1 is to determine the neuromuscular compartments within the GG, PCs, UES, and palatal muscles using current anatomical and histochemical criteria. The muscular organization, nerve supply patterns, banding patterns and types of the motor endplates, and fibertype distribution will be determined using whole-mount nerve staining (i.e., Sihler's stain), acetylcholinesterase and silver stain, and myofibrillar ATPase staining. Specific Aim 2 is to study the intrinsic properties of the muscle fibers in each of the muscles and/or compartments. The major and unusual MHC isoforms in muscle fibers in a given muscle and/or compartment will be detected using immunocytochemistry, whole muscle and/or single fiber electrophoresis, and immunoblotting techniques. The metabolic capacity of the MHC-based various fiber types in each muscle and/or compartment will be studied using enzyme-histochemical methods. Overall, the proposed studies will provide important data about the age-related, species-dependent and pathologically induced changes in the neuromuscular properties of the pharyngeal muscles. This knowledge will enhance our understanding of the anatomical and biochemical basis of the mechanisms involved in neuromuscular control of the pharyngeal swallowing, speech and respiration. The data may help to guide treatment strategies that are aimed at using implantable pharyngeal muscle nerve stimulators to alleviate dysphagia and airway obstruction during sleep.

描述（由申请人提供）：本次更新代表了先前申请的扩展，新的重点是探索咽扩张肌（genenoglossus， GG），咽收缩肌（PCs），上食管括约肌（UES）和腭肌的解剖和生化专门化：1)0-3岁和70-85岁的人类；2)人类特发性帕金森病（IPD）病理标本；3)成年猕猴。该应用程序的长期目标是提高我们对上呼吸道功能的神经肌肉控制以及导致吞咽困难和阻塞性睡眠呼吸暂停的机制的理解，以开发治疗这两种危及生命的疾病的新疗法。咽肌在维持上呼吸道通畅和咽吞咽中起着至关重要的作用。这些肌肉的功能障碍与上呼吸道疾病的发生有关。然而，这些疾病的发病机制仍然知之甚少。我们的初步研究表明，成人GG分为慢速水平室和快速斜室。pc和UES分别由慢内层和快外层组成，分别由IX和X神经支配。有趣的是，pc中组织化学定义的纤维层随着年龄的增长而变得模糊。另一个重要的发现是，成人咽肌中含有表达不寻常的肌球蛋白重链（MHC）异构体（慢强直和α -心脏）的肌纤维，其主要集中在慢水平GG和慢内层的pc。基于这些新的观察结果，我们假设成人咽部肌肉由于功能需求而特化，咽部肌肉纤维类型和MHC组成在正常人群的不同年龄组、正常成人和IPD之间以及人类和非人类灵长类之间存在差异。这些假设将通过以下两个具体目标进行检验。具体目的1是使用当前的解剖和组织化学标准确定GG、PCs、UES和腭肌内的神经肌肉室。肌肉组织、神经供应模式、运动终板的带状模式和类型以及纤维型分布将通过全坐垫神经染色（即席勒染色）、乙酰胆碱酯酶和银染色以及肌纤维atp酶染色来确定。具体目标2是研究每个肌肉和/或隔室中肌纤维的内在特性。将使用免疫细胞化学、全肌肉和/或单纤维电泳和免疫印迹技术检测给定肌肉和/或隔室肌肉纤维中主要和不寻常的MHC亚型。将使用酶组织化学方法研究每个肌肉和/或隔室中基于mhc的各种纤维类型的代谢能力。总的来说，拟议的研究将提供有关咽肌神经肌肉特性的年龄相关，物种依赖和病理诱导变化的重要数据。这些知识将增强我们对神经肌肉控制咽部吞咽、言语和呼吸机制的解剖学和生化基础的理解。这些数据可能有助于指导旨在使用植入式咽肌神经刺激器减轻睡眠期间吞咽困难和气道阻塞的治疗策略。