Anatomical Specializations of the Human Pharynx

人类咽部的解剖学特点

• 批准号: 8131664
• 负责人: LIANCAI MU
• 金额: $ 31.95万
• 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 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8131664
• 关键词: Academic Medical Centers; Affect; American; Anatomy; Area; Aspiration Pneumonia; Basal Ganglia; Biological; Bradykinesia; Cessation of life; Clinical; Cutaneous; Data; Databases; Deglutition; Deglutition Disorders; Development; Disease; Dopamine; Drooling; Enzymes; Epiglottis structure; Fiber; Functional disorder; Goals; Human; Laryngeal muscle structure; Lateral; Levodopa; Life; Limb structure; Link; Midbrain structure; Modification; Motor; Movement; Movement Disorders; Mucous Membrane; Muscle; Muscle Contraction; Muscle Fibers; Myosin Heavy Chains; Nerve; Nerve Degeneration; Nerve Fibers; Neuropeptides; Neurotransmitters; Operative Surgical Procedures; Oropharyngeal; Oropharyngeal Dysphagia; Parkinson Disease; Patients; Pattern; Peripheral; Peripheral Nervous System; Pharmaceutical Preparations; Pharyngeal structure; Pilot Projects; Presynaptic Terminals; Process; Reflex action; Research; Resistance; Saliva; Secondary to; Sensory; Staging; Structure; Substantia nigra structure; Symptoms; System; Techniques; Testing; Tissues; Tongue; Tremor; Vagus nerve structure; Widespread Disease; Work; afferent nerve; base; brain subcortex; density; dopaminergic neuron; effective therapy; experience; gastrointestinal symptom; gastrointestinal system; improved; intraepithelial; muscle form; neurochemistry; neuromuscular; novel; olfactory lobe; public health relevance; relating to nervous system; theories

DESCRIPTION (provided by applicant): This renewal is an expansion of work by the PI who recently relocated at Hackensack University Medical Center. This proposal focuses on exploring neural basis of dysphagia in idiopathic Parkinson's disease (PD). Dysphagia in PD is generally considered secondary to disease-related bradykinesia and rigidity. However, anti-PD drugs and surgical interventions, which are efficacious for the treatment of the primary clinical features affecting the limb function in PD, are not found to produce consistent or positive effects in the treatment of the dysphagia. These clinical findings suggest that oropharyngeal dysphagia in PD may not be linked solely to a reduction in basal ganglia dopamine activity. Other neurotransmitter systems or nondopaminergic mechanisms may also be involved. We hypothesized that oropharyngeal dysphagia in PD is associated with biological and neurochemical changes in the sensori-motor structures of the pharynx. The neural alterations in the sensory nerves could impair initiation of reflex swallowing, whereas those in the motor nerves could result in slowness of muscle contraction. We also hypothesized that the possible neuropathological changes such as degeneration-induced nerve fiber loss or a deduction in specific neuropeptide containing nerve fibers may occur in a nerve-dependent or tissue region-specific manner. Specifically, distinct regions of pharyngeal mucosa (lateral pharyngeal walls, epiglottis, postcricoid and arytenoids regions) and muscles (fast out layer of the pharyngeal constrictors) innervated by the X nerve are predominantly affected. This hypothesis gains support from our new findings which showed that both the pharyngeal mucosa triggering oropharyngeal swallowing and the swallowing-related fast out layer (FOL) of the pharyngeal constrictor muscles are innervated mainly by the branches derived from the X nerve. Importantly, our pilot studies also provided evidence for the selective involvement of the FOL in PD. We found that the FOL in PD pharynx became very slow as a result of fast-to-slow myosin heavy chain (MHC) transformation. These hypotheses will be tested with the following 2 specific aims. Specific Aim 1 is to explore morphometric and neurochemical changes in the sensory and motor nerves and axon terminals innervating the mucosa and muscle fibers in PD pharynx. Changes in the intraepithelial nerve fiber density and neuropeptide immunoreactive nerve fibers supplying the pharyngeal mucosa will be determined. Alterations in the motor nerves and endplates innervating the pharyngeal and tongue muscles will be also documented using quantitative techniques. Specific Aim 2 is to determine muscular alterations in the PD pharynx and tongue. The muscle mass, fiber size, enzyme- histochemical activities, fiber type and MHC expression patterns will be analyzed using morphological, immunocytochemical and electrophoretic techniques. The data are critical for a better understanding of the pathophysiological mechanisms of dysphagia in PD and for the development of novel therapies to treat this life-threatening disorder. PUBLIC HEALTH RELEVANCE: While idiopathic Parkinson's disease (PD) results in dysphagia which affects millions of Americans, the pathophysiological mechanisms of dysphagia are poorly understood. The proposed work is to test our hypothesis that PD-induced dysphagia is associated with degenerative changes in both the sensory and motor nerve fibers innervating swallowing-related structures in the oral and pharyngeal regions. This research will provide biological basis of neurogenic dysphagia which is critical for the development of novel therapies to treat this disorder.

描述（由申请人提供）：这项更新是最近搬迁到哈肯萨克大学医学中心的私家侦探工作的扩展。本研究旨在探讨特发性帕金森病（PD）患者吞咽困难的神经基础。PD患者的吞咽困难通常被认为是继发于疾病相关的运动迟缓和僵硬。然而，抗PD药物和手术干预对PD患者影响肢体功能的主要临床特征有效，但对吞咽困难的治疗却没有一致或积极的效果。这些临床发现表明PD患者的口咽吞咽困难可能不仅仅与基底神经节多巴胺活性降低有关。其他神经递质系统或非多巴胺能机制也可能参与其中。我们假设PD患者的口咽吞咽困难与咽部感觉运动结构的生物学和神经化学变化有关。感觉神经的改变会影响反射性吞咽的启动，而运动神经的改变会导致肌肉收缩缓慢。我们还假设可能的神经病理改变，如变性引起的神经纤维丢失或特定神经肽含有神经纤维的减少，可能以神经依赖或组织区域特异性的方式发生。具体来说，受X神经支配的咽部粘膜的不同区域（咽侧壁、会厌、环后和杓状区）和肌肉（咽部收缩肌的快出层）主要受到影响。我们的新发现支持了这一假设，即触发口咽吞咽的咽粘膜和咽部收缩肌与吞咽相关的快出层（FOL）主要受X神经分支的支配。重要的是，我们的试点研究也为FOL在PD中的选择性参与提供了证据。我们发现PD咽部的FOL由于快到慢的肌球蛋白重链（MHC）转化而变得非常缓慢。这些假设将通过以下两个具体目标进行检验。具体目的1：探讨PD咽部支配粘膜和肌纤维的感觉神经、运动神经和轴突末梢的形态和神经化学变化。上皮内神经纤维密度和供应咽粘膜的神经肽免疫反应性神经纤维的变化将被确定。在运动神经和终板支配咽部和舌肌的变化也将记录使用定量技术。具体目的2是确定PD患者咽部和舌头的肌肉变化。肌量、纤维大小、酶组织化学活性、纤维类型和MHC表达模式将使用形态学、免疫细胞化学和电泳技术进行分析。这些数据对于更好地理解PD患者吞咽困难的病理生理机制和开发治疗这种危及生命的疾病的新疗法至关重要。