Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (5): 933-939.doi: 10.4103/1673-5374.355746

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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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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