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

Neural Regeneration Research 2023年第5期18卷 933-939页

作者： Wen-Yuan Li Ling-Xiao Deng Feng-Guo Zhai Xiao-Yu Wang Zhi-Gang Li Ying Wang Institute of Neural Tissue Engineering Mudanjiang College of MedicineMudanjiangHeilongjiang ProvinceChina Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteIndiana University School of MedicineIndianapolisINUSA Department of Pharmacy Mudanjiang College of MedicineMudanjiangHeilongjiang ProvinceChina Department of General Surgery Hongqi HospitalMudanjiang College of MedicineMudanjiangHeilongjiang ProvinceChina

Chx10-expressing V2 a(Chx10+V2 a) spinal interneurons play a large role in the excitatory drive of motoneurons. Chemogenetic ablation studies have demonstrated the essential nature of Chx10+V2 a interneurons in the regulation of locomotor initiation, maintenance, alternation, speed, and rhythmicity. The role of Chx10+V2 a 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+V2 a 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+V2 a interneurons play an integral role in conferring locomotion, which integrates various corticospinal, mechanosensory, and interneuron pathways. Moreover, accumulating evidence suggests that Chx10+V2 a interneurons also play an important role in rhythmic patterning maintenance, leftright 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+V2 a 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+V2 a 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+V2 a interneurons transplanted in spinal cord injury foci.

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

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