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.

这次更新是最近在哈肯萨克大学医学院搬迁的PI工作的扩展 中心本研究旨在探讨原发性帕金森病（PD）吞咽障碍的神经基础。 PD中的吞咽困难通常被认为继发于疾病相关的运动迟缓和僵硬。然而，反- PD药物和手术干预，可有效治疗主要临床特征 影响PD肢体功能的药物，在治疗PD时未发现产生一致或积极的效果。 吞咽困难这些临床结果表明，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。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生物学和 咽部感觉运动结构的神经化学变化。感觉神经的变化 运动神经可使吞咽反射的起始减弱，而运动神经则可使吞咽反射减慢 肌肉收缩。我们还假设，可能的神经病理学变化，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减少可 以神经依赖性或组织区域特异性方式发生。具体来说，咽部的不同区域 粘膜（咽侧壁、会厌、环状软骨后和杓状软骨区域）和肌肉（咽后壁的快出层） 由X神经支配的咽缩肌）主要受到影响。这一假设获得 我们的新发现支持了这一点，即咽粘膜触发口咽 吞咽和咽缩肌的吞咽相关快出层（FOL）是 主要由X神经的分支支配。重要的是，我们的试点研究还提供了 FOL选择性参与PD的证据。我们发现PD咽部的FOL变得非常 由于肌球蛋白重链（MHC）由快到慢转化而变慢。这些假设将得到检验 有以下两个具体目标。具体目标1是探索在脑内的形态测量学和神经化学变化， 感觉神经和运动神经以及支配PD咽粘膜和肌纤维的轴突终末。 上皮内神经纤维密度和神经肽免疫反应阳性神经纤维的变化 将测定咽粘膜。运动神经和终板的改变支配 还将使用定量技术记录咽部和舌部肌肉。具体目标二是 确定PD咽部和舌部的肌肉变化。肌肉质量纤维大小酶- 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。这些数据对于更好地了解 PD患者吞咽困难的病理生理学机制，以及开发治疗这种疾病的新疗法 危及生命的疾病

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