Aging, Exercise and Mechanisms of Altered Tongue Function

有大量的证据表明，肌肉减少症，与年龄有关的肌肉大小的变化， 运动神经元、神经-肌肉、神经-肌肉和神经-肌肉之间的解剖和生理变化 连接和肌肉本身。除了四肢的骨骼肌， 毫无疑问发生在颅肌和支配它们的脑干神经元中。舌头的变化 肌肉和舌下神经运动神经元的结构和功能可能导致与年龄相关的衰老 吞咽和说话。然而，对年龄相关变化的病理生理学知之甚少 脑神经肌肉系统的一部分在我们的实验室里，我们发现舌头的变化与年龄有关， 肌肉，神经肌肉接头（NMJ），和舌下运动神经元及其突触能神经元 在啮齿动物模型中的神经调节输入。在拟议的研究中，我们计划使用渐进式 我们在清醒的大鼠中开发了阻力舌运动程序，以研究运动在 预防或逆转舌和舌下神经核内的年龄相关变化。我们的假设是 与年龄相关的舌下神经核的变化，以及去神经再支配过程， 是导致舌肌减少症的主要因素，这些过程可以通过以下方法预防或逆转： 锻炼的我们将通过比较生理学、形态学、生物化学和分子生物学来验证这一假设。 在年轻，中年和老年大鼠的舌肌和舌下神经运动神经元的参数， 与假运动对照组相比，拟议 研究有五个具体目标。在青年、中年和老年大鼠中，我们将确定：（1） 舌力和肌肉收缩特性随年龄和锻炼而变化， 预测舌肌变化的形态学、生物化学和分子变量 年龄和运动对舌的形态学和生化特性的影响 肌肉;（3）年龄和运动对神经肌肉连接形态的影响，（4）年龄的影响 和运动对舌下神经核神经元可塑性的影响;（5）神经营养因子在运动中的作用- 在年轻、中年和老年大鼠中诱导神经元可塑性。这项工作具有创新性和重要性 因为运动可能影响舌运动系统的神经保护作用的机制 很大程度上是未开发的。我们的神经肌肉模型是第一个评估行为锻炼效果的模型 颅运动神经元和舌头生理学的研究项目。此外，这项工作在提供一个 理解运动作为一种治疗干预的潜在益处的机制的基础 与年龄相关的颅肌变化

There is an overwhelming body of evidence that links sarcopenia, the age-related changes in muscle size, strength, and function, to anatomical and physiological changes within motoneurons, nerve-muscle connections, and the muscles themselves. In addition to skeletal muscle in the limbs, age-related changes undoubtedly occur in cranial muscles and the brainstem neurons that innervate them. Alterations in tongue muscle and hypoglossal motoneuron structure and function may contribute to the age-related decline in swallowing and speech. However, little is known about the pathophysiology underlying age-related changes in the cranial neuromuscular system. In our laboratories, we have found age-related changes in tongue muscles, the neuromuscular junction (NMJ), and in hypoglossal motoneurons and their serotonergic neuromodulatory inputs in a rodent model. In the proposed research, we plan to use a progressive resistance tongue exercise program we have developed in awake rats to investigate the role of exercise in preventing or reversing age-related changes within the tongue and hypoglossal nucleus. Our hypothesis is that age-associated changes in the hypoglossal nucleus, together with denervation-reinnervation processes, are major contributors to lingual sarcopenia, and that these processes can be prevented or reversed by exercise. We will test this hypothesis by comparing physiological, morphological, biochemical, and molecular parameters of tongue muscles and hypoglossal motoneurons in young, middle-aged, and old rats that have undergone behavioral tongue exercise versus those in a sham-exercise control group. The proposed research has 5 specific aims. In young, middle-aged and old rats, we will determine: (1) the degree to which behavioral tongue forces and muscle contractile properties change as a function of age and exercise, and morphological, biochemical, and molecular variables that are predictive of changes in tongue muscle contractile properties; (2) the effect of age and exercise on morphological and biochemical properties of tongue muscles; (3) the effect of age and exercise on morphology of nerve-muscle connections, (4) the effect of age and exercise on neuronal plasticity in the hypoglossal nucleus; and, (5) the role of neurotrophins in exercise- induced neuronal plasticity in young, middle-aged, and old rats. This work is innovative and important because the mechanisms by which exercise may impact neuroprotective effects in the lingual motor system are largely unexplored. Our neuromuscular model is the first to evaluate the effects of a behavioral exercise program on cranial motoneurons and tongue physiology. Further, this work is highly significant in providing a basis for understanding mechanisms underlying the putative benefits of exercise as a therapeutic intervention for age-related changes in cranial muscles.