Neuroplastic potential of exercise in the cranial sensorimotor system

描述（由申请人提供）：基于运动的疗法目前用于治疗声音和吞咽障碍，但没有明确了解改变颅神经肌肉系统的机制。例如，目前尚不清楚的是，以改善吞咽为目标的舌头练习是否只改变了目标结构（舌头）中的神经基质，还是这些练习也影响了其他与吞咽相关的（喉）结构（交叉训练）。也不清楚停止治疗后行为和神经可塑性的改变是否会持续。最近，神经可塑性原理在康复中的应用彻底改变了我们对治疗的看法，强调了改变行为和神经基质以创造持久效益的必要性。然而，在控制可能影响可塑性的因素（如遗传和环境差异）的同时，研究人类患者的神经基质是困难的。使用大鼠模型可以进行这些控制。这项研究旨在进一步了解运动在颅感觉运动系统中的神经可塑性潜力，最终的长期目标是指导有声音和吞咽问题的个体的护理。神经营养因子是神经可塑性的介质。我们实验室的研究表明，成年大鼠8周的舌头运动导致舌力增加和舌下核神经营养蛋白上调。然而，舌头锻炼是否在整个颅感觉运动系统和整个生命周期中产生持久和普遍的治疗效果尚不清楚。我们假设：1)舌头运动将在整个生命周期中上调颅感觉运动系统中的神经营养物质，并对舌部和喉部结构产生更大的影响

DESCRIPTION (provided by applicant): Exercise-based therapies are currently used to treat voice and swallowing disorders without a clear understanding of the mechanisms that alter the cranial neuromuscular system. For instance, it is not known if tongue exercises that target improved swallowing alter neural substrates in targeted structures (tongue) alone or if these exercises also affect other swallow-related (laryngeal) structures (cross-training). It is also unknown if behavioral and neuroplastic changes endure after therapy is discontinued. The recent application of principles of neuroplasticity to rehabilitation has revolutionized how we think about treatment, highlighting the need for change in both behavior and neural substrates for creating lasting benefits. It is difficult, however, to study neural substrates in human patiens while controlling for factors that may influence plasticity such as genetic and environmental differences. The use of a rat model allows these controls. The proposed research aims to further our understanding of the neuroplastic potential of exercise in the cranial sensorimotor system with the ultimate long-term goal of guiding care of individuals with voice and swallowing problems. Neurotrophins are mediators of neuroplasticity. Research from our laboratory has shown that 8 weeks of tongue exercise in adult rats leads to increased tongue forces and neurotrophin up-regulation in the hypoglossal nucleus. However, it is unknown if tongue exercise creates lasting and generalizable therapeutic benefits throughout the cranial sensorimotor system and across the lifespan. It is hypothesized that: 1) tongue exercise will up-regulate neurotrophins in the cranial sensorimotor system across the lifespan with greater effects in lingual versus laryngeal structures, and 2) that exercise effects will diminish when the exercise program is discontinued (detraining). We will test these hypotheses in a rat model by comparing behavioral and molecular neurotrophin parameters in rats of different ages that have undergone a tongue exercise program, a detraining program, or a control condition. The proposed research has 2 specific aims. In young adult and old rats, we will: 1) determine the effect of tongue exercise on neurotrophins and behavioral measures in the cranial sensorimotor system to examine cross-training effects and neuroplastic potential, and 2) examine the enduring effects of exercise by quantifying both neurotrophins and behavioral measures following a 2 or 4 week detraining period. The proposed research is significant because it will examine the cross-training and neuroplastic potential of exercise in the cranial sensorimotor system in both muscle and the central nervous system, along with the enduring effects of exercise (detraining) with the long term goal of using our results to guide current therapy timelines and protocols used in clinical populations with voice and swallowing problems.