Response of aging intrinsic laryngeal muscles to chronic electrical stimulation

老化的喉内肌对慢性电刺激的反应

• 批准号: 8663873
• 负责人: COLLEEN A MCMULLEN
• 金额: $ 31.56万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-22 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8663873
• 关键词: Aerobic; Affect; Age; Aging; Animal Model; Biochemistry; Chronic; Clinical Treatment; Complex; Data; Deglutition Disorders; Denervation; Development; Elderly; Electric Stimulation; Exercise; Exercise Physiology; Food; Foreign Bodies; Functional disorder; Human; Hybrids; Individual; Intervention; Laryngeal muscle structure; Larynx; Legitimacy; Life; Limb structure; Measures; Metabolic; Mitochondria; Modality; Modeling; Morbidity - disease rate; Morphology; Motor; Muscle; Muscle Fibers; Muscle Weakness; Muscle denervation procedure; Muscle rehabilitation; Nerve; Neuromuscular Diseases; Neuromuscular Junction; Norway; Parents; Phenotype; Phonation; Physiological; Physiology; Population; Protocols documentation; Rattus; Rehabilitation therapy; Research Project Grants; Risk; Skeletal Muscle; Source; Speech; Testing; Thyroarytenoid Muscle; Training; United States National Institutes of Health; Voice; Voice Disorders; Voice Quality; Work; age related; aged; base; cricoarytenoideus; density; design; efficacy testing; indexing; mortality; muscle form; neurophysiology; novel; prevent; programs; research study; response; sensorimotor system; therapy development; vocal cord; voice therapy

DESCRIPTION (provided by applicant): This application is in response to the NIH Research Project Grant (Parent R01) (PA-10-067). As individuals age, muscle weakness and the development of neuromuscular disorders have the potential to severely diminish the quality of one's life. The larynx is part of a complex sensorimotor system that serves as both a vibratory source for phonation and as a regulatory valving mechanism that protects the airway from the incursion of foreign bodies and food. In the elderly, age-related changes in the laryngeal muscles may compromise voice quality, impairing the ability of individuals to communicate and diminishing their ability to remain socially active and engaged. More significantly, laryngeal muscle dysfunction may contribute to the emergence of dysphagia and subsequent increases in the risk of aspiration, factors that contribute to higher rates of mortality and morbidity. Our preliminary findings indicate that the intrinsic laryngeal muscles have a unique phenotype that is significantly altered by age. More specifically, therapies for certain voice disorders contend to use common principles of skeletal muscle rehabilitation in the hope of increasing muscle mass, strength, and endurance. However, the rationale and applicability of limb muscle rehabilitation concepts to the laryngeal muscles has not been empirically tested. Therefore, this proposal has three principle objectives:(1) to use chronic electrical stimulation as a fictive endurance "exercise" program in aging rat laryngeal muscle; (2) to characterize the morphological changes consequent to the fictive exercise model; and (3) to provide the background data to eventually extend these findings to clinical treatments with humans using vocal exercises. We will test the central hypothesis that the physiology of aged laryngeal muscle can be modified as a function of chronically-induced activity using the Fisher 344-Brown Norway F1 hybrid rat model of aging. We will examine to what extent chronic electrical stimulation remodels the aging posterior cricoarytenoid (PCA, vocal fold abductor) and thyoarytenoid (TA, vocal fold adductor) laryngeal muscles. Specific Aim I will examine the effects of chronic electrical stimulation on muscle morphology in aging PCA and TA. Specific Aim 2 will test whether chronic stimulation modifies the metabolic capacity in the aging PCA and TA muscles. Specific Aim 3 will determine to what extent chronic nerve stimulation will reverse functional denervation in aging laryngeal muscles. These studies will be a first test of the applicability of limb muscle rehabilitation interventions intended to effectively alleviate, reverse and/or compensate for age-related dysfunction in the laryngeal muscles. This project will generate novel data to assist in the development of interventions aimed at preventing, reversing, and/or compensating for age-related dysfunction in the human larynx, providing a first step toward testing the efficacy and legitimacy of current voice disorder interventions.

描述（由申请人提供）：本申请是对NIH研究项目资助（父R 01）（PA-10-067）的回应。随着年龄的增长，肌肉无力和神经肌肉疾病的发展有可能严重降低一个人的生活质量。喉是一个复杂的感觉运动系统的一部分，它既是发声的振动源，又是保护气道免受异物和食物侵入的调节阀门机制。在老年人中，与年龄相关的喉部肌肉变化可能会损害声音质量，损害个人的沟通能力，并降低他们保持社交活跃和参与的能力。更重要的是，喉肌功能障碍可能导致吞咽困难的出现和随后的误吸风险增加，这些因素导致死亡率和发病率较高。我们的初步研究结果表明，喉内肌有一个独特的表型，是显着改变的年龄。更具体地说，某些声音障碍的治疗方法试图使用骨骼肌康复的共同原则，希望增加肌肉质量，力量和耐力。然而，喉肌肢体肌肉康复概念的基本原理和适用性还没有经过实证检验。因此，该提议具有三个主要目标：（1）使用慢性电刺激作为老化大鼠喉肌中的虚构耐力“锻炼”程序;（2）表征虚构锻炼模型引起的形态学变化;以及（3）提供背景数据以最终将这些发现扩展到使用发声锻炼的人类临床治疗。我们将测试中心的假设，即老年喉肌的生理学可以修改为功能的慢性诱导的活动，使用Fisher 344-Brown Norway F1杂交大鼠模型的老化。我们将研究慢性电刺激在多大程度上重塑了老化的环杓后肌（PCA，声带外展肌）和甲杓肌（TA，声带内收肌）喉肌。具体目的我将研究慢性电刺激对老年PCA和TA肌肉形态的影响。具体目标2将测试慢性刺激是否改变老化PCA和TA肌肉的代谢能力。具体目标3将确定慢性神经刺激将在多大程度上逆转老化喉肌的功能性去神经支配。这些研究将首次测试肢体肌肉康复干预措施的适用性，旨在有效缓解，逆转和/或补偿喉肌中与年龄相关的功能障碍。该项目将产生新的数据，以帮助开发旨在预防、逆转和/或补偿人类喉部年龄相关功能障碍的干预措施，为测试当前嗓音障碍干预措施的有效性和合法性迈出第一步。