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首页> 外文期刊>Neuroscience: An International Journal under the Editorial Direction of IBRO >TARGETING THE MOTOR END PLATES IN THE MOUSE HINDLIMB GIVES ACCESS TO A GREATER NUMBER OF SPINAL CORD MOTOR NEURONS: AN APPROACH TO MAXIMIZE RETROGRADE TRANSPORT
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TARGETING THE MOTOR END PLATES IN THE MOUSE HINDLIMB GIVES ACCESS TO A GREATER NUMBER OF SPINAL CORD MOTOR NEURONS: AN APPROACH TO MAXIMIZE RETROGRADE TRANSPORT

机译：在小鼠后肢中定位运动终极板可提供更多数量的脊髓运动神经元：最大限度地减少逆行运输的方法

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摘要

Lower motor neuron dysfunction is one of the most debilitating neurological conditions and, as such, significantly impacts on the quality of life of affected individuals. Within the last decade, the engineering of mouse models of lower motor neuron diseases has facilitated the development of new therapeutic scenarios aimed at delaying or reversing the progression of these conditions. In this context, motor end plates (MEPs) are highly specialized regions on the skeletal musculature that offer minimally invasive access to the pre-synaptic nerve terminals, henceforth to the spinal cord motor neurons. Transgenic technologies can take advantage of the relationship between the MEP regions on the skeletal muscles and the corresponding motor neurons to shuttle therapeutic genes into specific compartments within the ventral horn of the spinal cord. The first aim of this neuroanatomical investigation was to map the details of the organization of the MEP zones for the main muscles of the mouse hindlimb. The hindlimb was selected for the present work, as it is currently a common target to challenge the efficacy of therapies aimed at alleviating neuromuscular dysfunction. This MEP map was then used to guide series of intramuscular injections of Flu-oro-Gold (FG) along the muscles' MEP zones, therefore revealing the distribution of the motor neurons that supply them. Targeting the entire MEP regions with FG increased the somatic availability of the retrograde tracer and, consequently, gave rise to FG-positive motor neurons that are organized into rostro-caudal columns spanning more spinal cord segments than previously reported. The results of this investigation will have positive implications for future studies involving the somatic delivery and retrograde transport of therapeutic transgenes into affected motor neurons. These data will also provide a framework for transgenic technologies aiming at maintaining the integrity of the neuromuscular junction for the treatment of lower motor neuron dysfunctions.
机译：下运动神经元功能障碍是最使人衰弱的神经系统疾病之一，因此，对患病个体的生活质量产生重大影响。在过去的十年中，下运动神经元疾病的小鼠模型的设计促进了旨在延缓或逆转这些疾病进展的新治疗方案的开发。在这种情况下，运动终板（MEP）是骨骼肌组织上高度专门化的区域，可提供对突触前神经末梢（此后至脊髓运动神经元）的微创访问。转基因技术可以利用骨骼肌MEP区域与相应运动神经元之间的关系，将治疗基因穿梭到脊髓腹角内的特定区域。这种神经解剖学研究的首要目的是为小鼠后肢的主要肌肉绘制MEP区组织的细节图。选择后肢进行当前工作是因为它目前是挑战缓解神经肌肉功能障碍的疗法功效的共同目标。然后，该MEP图用于沿着肌肉的MEP区域引导一系列肌肉注射Flu-oro-Gold（FG），因此揭示了为其提供运动神经元的分布。用FG靶向整个MEP区域可增加逆行示踪剂的体细胞利用率，因此，产生了FG阳性运动神经元，这些神经元被组织成横贯脊髓的节尾柱，比以前报道的更多。这项研究的结果将对涉及治疗性转基因向受影响的运动神经元的体细胞递送和逆行转运的未来研究产生积极影响。这些数据还将为转基因技术提供一个框架，旨在维持神经肌肉接头的完整性，以治疗下运动神经元功能障碍。

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