Anatomical Specializations of the Human Pharynx

人类咽部的解剖学特点

• 批准号: 8311052
• 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 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8311052
• 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; relating to nervous system; theories

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 neuochemical 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.

这种续约是PI的扩展 中心。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。但是，反 - PD药物和手术干预措施，可有效治疗主要临床特征 影响PD中的肢体功能，没有发现在治疗中产生一致或积极的影响 吞咽困难。这些临床发现表明，PD中的口咽吞咽困难可能不仅与A有关 基底神经节多巴胺活性的降低。其他神经递质系统或非巴氨基能机制 也可能参与其中。我们假设PD中的口咽吞咽困难与生物学和 咽的感觉运动运动结构的神经化学变化。感觉的神经改变 神经可能会损害反射吞咽的启动，而运动神经中的那些可能会导致慢跑 肌肉收缩。我们还假设可能的神经病理学变化，例如 变性引起的神经纤维损失或含有特定神经肽的神经纤维的扣除可能 以神经依赖或组织特异性方式发生。具体而言，咽部的不同区域 粘膜（外侧咽壁，上皮壁，后乳状细胞和芳香类动物区域）和肌肉（快速向外层的层 由X神经支配的咽部收缩物主要受到影响。这个假设获得了 我们的新发现的支持表明，两个咽粘膜都会触发口咽 吞咽和与吞咽相关的快速外层（fol）（咽部收缩肌肉） 主要由源自X神经的分支支配。重要的是，我们的试点研究也提供了 FOL参与PD的证据。我们发现pd pharynx中的FOL变得非常 由于快速慢的肌球蛋白重链（MHC）转化而慢。这些假设将进行测试 以下两个特定目标。具体目的1是探索形态计量学和神经化学的变化 感官和运动神经和轴突末端在PD咽中支配粘膜和肌肉纤维。 上皮内神经纤维密度和神经肽免疫反应神经纤维的变化 将确定咽粘膜。运动神经的改变和终止底层支配 还将使用定量技术记录咽部和舌头肌肉。具体目标2是 确定PD咽和舌头的肌肉改变。肌肉质量，纤维尺寸，酶 - 组织化学活动，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。数据对于更好地理解 PD中吞咽困难的病理生理机制以及用于治疗这种治疗的新型疗法 威胁生命的障碍。

项目成果

Adult human upper esophageal sphincter contains specialized muscle fibers expressing unusual myosin heavy chain isoforms.

成人上食管括约肌含有表达不寻常肌球蛋白重链亚型的特殊肌纤维。

• DOI: 10.1369/jhc.6a7084.2006
• 发表时间: 2007
• 期刊: The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
• 作者: Mu,Liancai;Wang,Jun;Su,Hungxi;Sanders,Ira
• 通讯作者: Sanders,Ira

Human tongue neuroanatomy: Nerve supply and motor endplates.

• DOI: 10.1002/ca.21011
• 发表时间: 2010-10
• 期刊: CLINICAL ANATOMY
• 影响因子: 2.4
• 作者: Mu, Liancai;Sanders, Ira
• 通讯作者: Sanders, Ira

Newly revealed cricothyropharyngeus muscle in the human laryngopharynx.

新发现的人类喉咽部的环甲咽肌。

• DOI: 10.1002/ar.20727
• 发表时间: 2008
• 期刊: Anatomical record (Hoboken, N.J. : 2007)
• 作者: Mu,Liancai;Sanders,Ira
• 通讯作者: Sanders,Ira

Sihler's whole mount nerve staining technique: a review.

Sihler 的整体神经染色技术：回顾。

• DOI: 10.3109/10520290903048384
• 发表时间: 2010-02
• 期刊: BIOTECHNIC & HISTOCHEMISTRY
• 影响因子: 1.6
• 作者: Mu, L.;Sanders, I.
• 通讯作者: Sanders, I.

Alpha-synuclein pathology and axonal degeneration of the peripheral motor nerves innervating pharyngeal muscles in Parkinson disease.

• DOI: 10.1097/nen.0b013e3182801cde
• 发表时间: 2013-02
• 期刊: Journal of neuropathology and experimental neurology
• 影响因子: 3.2
• 作者: Mu L;Sobotka S;Chen J;Su H;Sanders I;Adler CH;Shill HA;Caviness JN;Samanta JE;Beach TG;Arizona Parkinson’s Disease Consortium
• 通讯作者: Arizona Parkinson’s Disease Consortium