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）：此更新是PI的扩展，最近在Hackensack University Center Center搬迁。该提案着重于探索特发性帕金森氏病（PD）中吞咽困难的神经基础。 PD中的吞咽困难通常被认为是与疾病相关的头肌关系和刚性的继发性。然而，没有发现抗PD药物和手术干预措施可有效治疗影响PD中肢体功能的主要临床特征，在治疗吞咽困难的治疗中不会产生一致或积极的影响。这些临床发现表明，PD中的口咽性吞咽困难可能不仅与降低基底神经节多巴胺活性有关。也可能涉及其他神经递质系统或非氨基胺能机制。我们假设PD中的口咽吞咽困难与咽的感觉运动运动结构的生物学和神经化学变化有关。感觉神经的神经改变可能会损害反射吞咽的开始，而运动神经中的神经可能会导致肌肉收缩的缓慢。我们还假设，可能以神经纤维丧失的神经纤维丧失等神经病理学变化或含有神经纤维的特定神经肽的扣除可能以神经依赖性或组织特异性方式发生。具体而言，咽粘膜（外侧咽壁，上皮壁，蛋白质后和芳族型区域）和肌肉（咽部约束的快速层）的不同区域主要受到影响。这一假设从我们的新发现获得了支持，这些发现表明，咽粘膜触发口咽吞咽和吞咽相关的快速外层（fol）（fol），主要由源自X神经衍生的分支支配。重要的是，我们的试点研究还为FOL参与PD提供了证据。我们发现，由于快速慢肌球蛋白重链（MHC）转换，PD咽中的FOL变得非常慢。这些假设将通过以下两个特定目标进行测试。具体目的1是探索感觉神经和轴突末端的形态和神经化学变化，该末端将粘膜和肌肉纤维支配在PD咽中。将确定上皮内神经纤维密度的变化和供应咽粘膜的神经肽免疫反应性神经纤维的变化。运动神经的改变和终结术的咽喉和舌头肌肉也将使用定量技术记录。具体目标2是确定PD咽和舌头的肌肉改变。将使用形态，免疫细胞化学和电泳技术分析肌肉质量，纤维大小，组织化学活性，纤维类型和MHC表达模式。数据对于更好地理解PD中吞咽困难的病理生理机制以及开发新的危及生命障碍的新疗法至关重要。 公共卫生相关性：虽然特发性帕金森氏病（PD）会导致吞咽困难，从而影响数百万美国人，但吞咽困难的病理生理机制知之甚少。拟议的工作是测试我们的假设，即PD诱导的吞咽困难与口腔和咽部区域中吞咽相关结构的感觉和运动神经纤维的退化性变化有关。这项研究将为神经源性吞咽困难提供生物学基础，这对于开发这种疾病的新疗法至关重要。