Exercise as a Treatment for Tongue Weakness in Aged Rats

运动治疗老年大鼠舌头无力

• 批准号: 6557709
• 负责人: NADINE P CONNOR
• 金额: $ 28.93万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-08 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6557709
• 关键词: SDS polyacrylamide gel electrophoresis; Schwann cells; age difference; aging; axon; confocal scanning microscopy; disease /disorder model; exercise; hypoglossal nerve; immunocytochemistry; laboratory rat; muscle contraction; musculoskeletal disorder therapy; myosins; neuroeffector; neuromuscular junction; neuromuscular stimulator; nonhuman therapy evaluation; protein isoforms; protein quantitation /detection; sarcopenia; statistics /biometry; stimulus /response; tissue /cell preparation; tongue

DESCRIPTION (provided by applicant): Fatigue and weakness are common complaints of elderly people related to sarcopenia, or the loss of skeletal muscle mass, organization, and strength. Little is known concerning the pathophysiology and age-related sequelae of sarcopenia in muscles of the head and neck. This knowledge is important inasmuch as alterations in muscle character may underlie deficits in speech and swallowing, which are significant clinical problems in elderly people. The tongue has a vital role in speech and swallowing, and poor lingual control is associated with both speech and swallowing impairment. However, muscles of the tongue have been understudied. Our hypothesis is that age-related alterations in tongue function are based upon naturally occurring denervation-reinnervation processes, and that these processes can be reversed or prevented via exercise. This hypothesis will be tested in a rat model by comparing physiological, molecular, and histological parameters of old rat tongue muscles with young muscles, and with old tongue muscles that have undergone chronic nerve stimulation to model exercise. The proposed research has 2 specific aims: (1) To quantify changes in neuromuscular morphology predictive of age-related tongue weakness; and (2) To determine underlying morphological and physiological changes induced by tongue exercise in old rats. Physiological experiments will be performed in vivo in the tongue in young rats and in 2 groups of older rats. In the same animals, molecular analyses of myosin heavy chain expression, and histological analyses of neuromuscular junctions will be performed. Exercise will be modeled via bilateral chronic stimulation of the hypoglossal nerves. Analyses of covariance (a combination of analysis of variance and regression) will be used to determine the degree to which muscle contractile properties can be predicted from molecular and histological characteristics. Further analyses of variance will be performed to compare the physiological, molecular, and histological variables of interest as a function of age group (Specific Aim 1) or age by exercise (Specific Aim 2). This work is innovative and important in establishing potential morphological bases for the alterations in physiological function observed with tongue muscle senescence. Further, this work will be highly significant in discovering a neuromuscular basis for the putative benefits of exercise in the prevention and treatment of age-related swallowing impairment.

描述（由申请人提供）：疲劳和弱点是与肌肉减少症有关的老年人的常见抱怨，或者是骨骼肌质量，组织和力量的丧失。关于头部和颈部肌肉中肌肉减少症的病理生理学和与年龄相关的后遗症知之甚少。这种知识很重要，因为肌肉特征的改变可能是言语和吞咽的缺陷，这在老年人中是重大的临床问题。舌头在言语和吞咽中具有至关重要的作用，舌头控制不佳与言语和吞咽障碍有关。但是，舌头的肌肉已经被研究了。我们的假设是，与年龄相关的舌头功能的改变是基于天然发生的神经连接过程，并且可以通过运动来逆转或预防这些过程。该假设将在大鼠模型中通过比较旧大鼠舌头肌肉的生理，分子和组织学参数与年轻肌肉的生理，分子和组织学参数，以及具有经历慢性神经刺激的旧舌肌与模型运动。拟议的研究具有2个具体目的：（1）量化神经肌肉形态的变化可预测与年龄相关的舌头弱点； （2）确定旧大鼠舌运动引起的基本形态和生理变化。生理实验将在年轻大鼠和2组老鼠的舌头中在体内进行。在相同的动物中，将对肌球蛋白重链表达进行分子分析，并将对神经肌肉连接的组织学分析进行。运动将通过双侧慢性刺激降压神经进行建模。协方差的分析（方差分析和回归分析）将用于确定可以从分子和组织学特征中预测肌肉收缩特性的程度。将进行进一步的方差分析，以比较感兴趣的生理，分子和组织学变量作为年龄组的函数（特定的目标1）或通过锻炼年龄（特定目标2）。这项工作对于建立潜在的形态基础是创新的，并且很重要，以改变舌肌衰老观察到的生理功能的改变。此外，这项工作将在发现锻炼的假定益处在预防和治疗与年龄有关的吞咽障碍方面的假定益处的神经肌肉基础上非常重要。