Pre-habilitation of Aged and Young Neuromuscular Systems

描述（由申请人提供）：已经确定，与年轻人相比，老年人的废用导致更大的神经肌肉损害。这对老年人来说是一个复杂的风险，因为他们不仅比年轻人更容易患上导致肌肉卸载（废用）的疾病和痛苦，而且由于废用，他们也遭受了更多的神经肌肉系统重塑。拟议项目的总体目标是确定“前hasting”-卸载前的身体活动-在缓和废用相关的神经肌肉系统改变的影响方面的功效。年轻的成年大鼠和老年大鼠都将作为未处理的对照或进行四周的肌肉卸载。暴露于卸货的动物中有一半将在卸货前参加两周的预防性运动。该研究项目的具体目标是：1）确定预刺激减弱神经肌肉系统中观察到的负适应的能力（肌肉纤维，神经肌肉接头），2）确定老化对预收缩功效的影响，3）评估NCAM表达-突触调节分子-在神经肌肉接头的形态重塑中的关系，和4）确定Synpatotagmin（神经传递过程中囊泡释放所必需的蛋白质）表达的年龄特异性变化在卸载后（有和没有前激素）是否明显。所收集的数据将提供重要的新的和有用的见解有关的潜力，pre-hasting，以减轻卸载引起的干扰，在神经肌肉系统的年轻人和老年人，以及细胞机制，可能有助于这种姑息性的影响。

DESCRIPTION (provided by applicant): It has been established that disuse results in greater neuromuscular detriment among the aged than among young adults. This presents a compounded risk to the aged since not only are they more likely to suffer from maladies and afflictions that result in muscle unloading (disuse) than the young, but they also suffer more remodeling of the neuromuscular system consequent to that disuse. The overall goal of the proposed project is to determine the efficacy of "pre-habilitation" - physical activity prior to unloading - in moderating the effects of disuse related alteration of the neuromuscular system. Both young adult and aged rats will either serve as untreated controls or be subjected to four weeks muscle unloading. Half of those animals exposed to unloading will participate in pre-habilitative exercise for two weeks prior to unloading. The specific aims of the research project are: 1) to determine the capacity of pre-habilitation to attenuate the negative adaptations observed in the neuromuscular system (muscle fibers, neuromuscular junctions) following unloading, 2) to ascertain the impact of aging on the efficacy of pre-habilitation, 3) to assess the relationship of NCAM expression - a synaptic regulatory molecule - in the morphological remodeling of the neuromuscular junction, and 4) to determine whether age-specific changes in the expression of Synpatotagmin - a protein essential to vesicular release during neurotransmission - are evident following unloading (with and without pre-habilitation). The data gathered will provide important new and useful insight regarding the potential of pre-habilitation to mitigate unloading induced disturbances in the neuromuscular system of young adults and the elderly, as well as the cellular mechanisms that may contribute to this palliative effect.