中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (5): 933-939.doi: 10.4103/1673-5374.355746

• 综述:脊髓损伤修复保护与再生 •    下一篇

Chx10+V2a中间神经元在运动调节和脊髓损伤治疗中的作用

  

  • 出版日期:2023-05-15 发布日期:2022-10-31
  • 基金资助:
    国家自然科学基金(81870977)，中国黑龙江省自然科学基金(JQ2021H004)，牡丹江医学院博士研究基金(2021-KYYWF-0469)，黑龙江省高校基础研究基金(2021-KYYWFMY-0011)

Chx10+V2a interneurons in spinal motor regulation and spinal cord injury

Wen-Yuan Li1, Ling-Xiao Deng2, Feng-Guo Zhai3, Xiao-Yu Wang1, Zhi-Gang Li4, *, Ying Wang1, *   

  1. 1Institute of Neural Tissue Engineering, Mudanjiang College of Medicine, Mudanjiang, Heilongjiang Province, China;  2Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA;  3Department of Pharmacy, Mudanjiang College of Medicine, Mudanjiang, Heilongjiang Province, China;  4Department of General Surgery, Hongqi Hospital, Mudanjiang College of Medicine, Mudanjiang, Heilongjiang Province, China 
  • Online:2023-05-15 Published:2022-10-31
  • Contact: Ying Wang, PhD, yingwang2016@sina.com; Zhi-Gang Li, MD, lizhigang120@sohu.com.
  • Supported by:
    The work was supported by the National Natural Science Foundation of China, No. 81870977 (to YW), the Natural Science Foundation of Heilongjiang Province of China, No. JQ2021H004 (to YW), and PhD research foundation of Mudanjiang Medicine College, No. 2021-MYBSKY-039 (to WYL), Fundamental Research Funds for Heilongjiang Provincial Universities, No. 2021-KYYWF-0469 (to WYL).

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摘要：

Chx10阳性特异性标记的V2a中间神经元(Chx10+V2a)在脊髓运动神经元(MN)的兴奋性驱动中发挥重要作用。目前已有研究通过化学遗传消融方法证实Chx10+V2a参与运动起始、维持、交替、速度和节律调控过程。因此其在运动和自主神经系统调节中具有重要作用。然而目前Chx10+V2a在脊髓运动调节和脊髓损伤中的作用尚未阐明。文章介绍了Chx10+V2a中间神经元的起源、分子特征和功能作用，重点阐述其在脊髓损伤发病机制中的作用。Chx10+V2a功能多样特性在很大程度上归因于募集在多种脊髓神经环路中。Chx10+V2a发挥运动信息整合作用，整合各种皮质脊髓、机械感觉和中间神经通路，大量证据表明Chx10 V2a在调控CPG和运动模式生成中发挥节律维持、交替调节作用。因此大量研究者认为损伤后移植和内在调控V2a中间神经元可作为一种有效脊髓损伤治疗策略。最后文章回顾了应用衍生和刺激/移植Chx10+V2a中间神经元作为治疗脊髓损伤策略的最新临床前研究进展发现，Chx10+V2a可作为脊髓损伤的新型治疗靶点。未来优化策略可聚焦于移植Chx10+V2a中间神经元在脊髓损伤灶中的生存能力、成熟度和功能整合。

https://orcid.org/0000-0002-5632-486X (Ying Wang); https://orcid.org/0000-0002-6751-2225 (Zhi-Gang Li)

关键词: 轴突, 中枢神经系统, Chx10, 中枢模式发生器, 分化, 中间神经元, 运动神经元, 本体脊髓, 脊髓损伤, 治疗, 转录因子, 移植, V2a神经元

Abstract:

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.

Key words: axons, central nervous system, central pattern generator, Chx10, differentiation, interneurons, locomotion, motor neurons, propriospinal, spinal cord injuries, therapy, transcription factor, transplantation, V2a neuron