Li Wen-Yuan, Deng Ling-Xiao, Zhai Feng-Guo, Wang Xiao-Yu, Li Zhi-Gang, Wang Ying
Institute of Neural Tissue Engineering, Mudanjiang College of Medicine, Mudanjiang, Heilongjiang Province, China.
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Neural Regen Res. 2023 May;18(5):933-939. doi: 10.4103/1673-5374.355746.
Chx10-expressing V2a (Chx10+V2a) spinal interneurons play a large role in the excitatory drive of motoneurons. Chemogenetic ablation studies have demonstrated the essential nature of Chx10+V2a interneurons in the regulation of locomotor initiation, maintenance, alternation, speed, and rhythmicity. The role of Chx10+V2a interneurons in locomotion and autonomic nervous system regulation is thought to be robust, but their precise role in spinal motor regulation and spinal cord injury have not been fully explored. The present paper reviews the origin, characteristics, and functional roles of Chx10+V2a interneurons with an emphasis on their involvement in the pathogenesis of spinal cord injury. The diverse functional properties of these cells have only been substantiated by and are due in large part to their integration in a variety of diverse spinal circuits. Chx10+V2a interneurons play an integral role in conferring locomotion, which integrates various corticospinal, mechanosensory, and interneuron pathways. Moreover, accumulating evidence suggests that Chx10+V2a interneurons also play an important role in rhythmic patterning maintenance, left-right alternation of central pattern generation, and locomotor pattern generation in higher order mammals, likely conferring complex locomotion. Consequently, the latest research has focused on postinjury transplantation and noninvasive stimulation of Chx10+V2a interneurons as a therapeutic strategy, particularly in spinal cord injury. Finally, we review the latest preclinical study advances in laboratory derivation and stimulation/transplantation of these cells as a strategy for the treatment of spinal cord injury. The evidence supports that the Chx10+V2a interneurons act as a new therapeutic target for spinal cord injury. Future optimization strategies should focus on the viability, maturity, and functional integration of Chx10+V2a interneurons transplanted in spinal cord injury foci.
表达Chx10的V2a（Chx10+V2a）脊髓中间神经元在运动神经元的兴奋性驱动中发挥着重要作用。化学遗传学消融研究已经证明了Chx10+V2a中间神经元在运动起始、维持、交替、速度和节律调节中的本质作用。Chx10+V2a中间神经元在运动和自主神经系统调节中的作用被认为是强大的，但其在脊髓运动调节和脊髓损伤中的精确作用尚未得到充分探索。本文综述了Chx10+V2a中间神经元的起源、特征和功能作用，重点关注它们在脊髓损伤发病机制中的参与情况。这些细胞的多种功能特性仅在很大程度上通过它们整合到各种不同的脊髓回路中得到证实。Chx10+V2a中间神经元在赋予运动能力方面发挥着不可或缺的作用，运动整合了各种皮质脊髓、机械感觉和中间神经元通路。此外，越来越多的证据表明，Chx10+V2a中间神经元在高等哺乳动物的节律模式维持、中枢模式发生器的左右交替以及运动模式生成中也发挥着重要作用，可能赋予复杂的运动能力。因此，最新的研究集中在将Chx10+V2a中间神经元损伤后移植和非侵入性刺激作为一种治疗策略，特别是在脊髓损伤方面。最后，我们综述了这些细胞在实验室衍生以及刺激/移植作为脊髓损伤治疗策略方面的最新临床前研究进展。证据支持Chx10+V2a中间神经元可作为脊髓损伤的新治疗靶点。未来的优化策略应集中在移植到脊髓损伤病灶的Chx10+V2a中间神经元的活力、成熟度和功能整合上。
