中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (2): 364-367.doi: 10.4103/1673-5374.346544

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

烟碱乙酰胆碱有助于脊髓损伤后运动恢复但非康复训练促进运动功能恢复所必需

  

  • 出版日期:2023-02-15 发布日期:2022-08-08
  • 基金资助:
    伯克基金会和美国国立卫生研究院共同基金;纽约州卫生部脊髓损伤研究委员会博士后奖学金

Nicotinic acetylcholine signaling is required for motor learning but not for rehabilitation from spinal cord injury

Yue Li1, †, Edmund R. Hollis II1, 2, *   

  1. 1Burke Neurological Institute, White Plains, NY, USA; 2Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA
  • Online:2023-02-15 Published:2022-08-08
  • Contact: Edmund R. Hollis II, PhD, edh3001@med.cornell.edu.
  • Supported by:
    This study was supported by the Burke Foundation and the National Institutes of Health Common Fund, No. DP2 NS106663 (to ERH); the New York State Department of Health Spinal Cord Injury Research Board Postdoctoral Fellowship, No. C32633GG (to YL).

摘要:

脊髓损伤的治疗方法是有限的,许多方法依赖于加强残余的神经元功能,并通过康复训练促进功能的恢复。康复训练的重点是恢复因受伤而失去的运动功能。脊髓损伤后以前习得动作的康复是否涉及运动学习的分子机制;或者是否功能恢复涉及到以前训练过的运动环路,而不需要新的学习仍然是需要进一步探讨的问题。实验中,随机给予小鼠腹腔注射烟碱拮抗剂麦克美拉明美加明(MEC),α7 神经元烟碱型乙酰胆碱受体 (α7nAChR) 的特异性拮抗剂甲基牛扁亭柠檬酸盐(MLA)或对照溶质(正常生理盐水),然后进行C5颈部脊髓背柱损伤致脊髓不完全损伤后的康复训练。实验结果显示,烟碱型乙酰胆碱信号是脊髓损伤后运动学习所必需的,但对于伤后康复训练的运动功能的恢复并不必需。结果表明,脊髓损伤后运动学习与康复训练后运动功能恢复间的分子机制存在差异。

https://orcid.org/0000-0002-9594-5802 (Yue Li); https://orcid.org/0000-0002-4535-4668 (Edmund R. Hollis II)

Abstract: Therapeutic intervention for spinal cord injury is limited, with many approaches relying on strengthening the remaining substrate and driving recovery through rehabilitative training. As compared with learning novel compensatory strategies, rehabilitation focuses on restoring movements lost to injury. Whether rehabilitation of previously learned movements after spinal cord injury requires the molecular mechanisms of motor learning, or if it engages previously trained motor circuits without requiring novel learning remains an open question. In this study, mice were randomly assigned to receive intraperitoneal injection with the pan-nicotinic, non-competitive antagonist mecamylamine and the nicotinic α7 subunit selective antagonist methyllycaconitine citrate salt or vehicle (normal saline) prior to motor learning assays, then randomly reassigned after motor learning for rehabilitation study post-injury. Cervical spinal cord dorsal column lesion was used as a model of incomplete injury. Results of this study showed that nicotinic acetylcholine signaling was required for motor learning of the single pellet-reaching task but it was dispensable for the rehabilitation of the same task after injury. Our findings indicate that critical differences exist between the molecular mechanisms supporting compensatory motor learning strategies and the restoration of behavior lost to spinal cord injury.

Key words: acetylcholine, basal forebrain, corticospinal tract, dorsal column lesion, mecamylamine, methyllycaconitine, motor control, rehabilitation, rotarod, single pellet-reaching task