Neuroplastic potential of exercise in the cranial sensorimotor system

描述(申请人提供)：基于运动的疗法目前用于治疗发声和吞咽障碍，但对改变脑神经肌肉系统的机制没有明确的了解。例如，目前尚不清楚以改善吞咽为目标的舌操是否只改变了靶向结构(舌头)中的神经基质，或者这些练习是否也影响了其他与吞咽相关的(喉)结构(交叉训练)。在停止治疗后，行为和神经可塑性的变化是否会持续也是未知的。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，强调了为创造持久的好处，行为和神经基础都需要改变。然而，在控制遗传和环境差异等可能影响可塑性的因素的同时，研究人类患者的神经基质是困难的。使用老鼠模型可以进行这些控制。这项拟议的研究旨在加深我们对运动在颅骨感觉运动系统中的神经再生潜能的理解，最终的长期目标是指导有声音和吞咽问题的个人的护理。神经营养因子是神经可塑性的介体。我们实验室的研究表明，成年大鼠进行8周的舌功训练后，舌力增加，舌下神经核神经营养素上调。然而，舌头运动是否在整个颅骨感觉运动系统和整个生命周期内产生持久和可推广的治疗益处尚不清楚。假设：1)舌头运动将在一生中上调颅骨感觉运动系统中的神经营养因子，对舌部结构的影响比对喉部结构的影响更大；2)当 运动计划被终止(取消训练)。我们将通过比较不同年龄段的大鼠的行为和分子神经营养因子参数，在大鼠模型中检验这些假设，这些大鼠接受了舌头锻炼计划、去训练计划或控制条件。这项拟议的研究有两个具体目标。在青壮年和老年大鼠中，我们将：1)确定舌运动对神经营养因子和颅感觉运动系统中的行为测量的影响，以检查交叉训练的效果和神经再生潜能；2)通过量化2或4周的脱训期后的神经营养因子和行为测量来检验运动的持久效应。这项拟议的研究意义重大，因为它将检查运动在肌肉和中枢神经系统的颅骨感觉运动系统中的交叉训练和神经再生潜力，以及运动(去训练)的持久影响，长期目标是使用我们的结果来指导当前用于语音和吞咽问题临床人群的治疗时间表和方案。

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.