化学遗传刺激动力输出和隔膜活动
Ethan S Benevides1,2, Prajwal P Thakre1,2,3, Sabhya Rana1,2,3
1Department of Physical Therapy, University of Florida, Gainesville, FL, 32601.
bioRxiv : the preprint server for biology
|April 25, 2024
概括
针对专门由设计药物 (DREADDs) 激活的设计受体到特定的脊髓神经元,有效地刺激了隔膜激活和增加了动物模型中的呼吸量. 这种方法对治疗呼吸系统功能障碍有希望.
科学领域:
- 神经科学是一个神经科学.
- 呼吸系统生理学 呼吸系统生理学
- 生物技术是生物技术.
背景情况:
- 呼吸机运动输出受损是神经退行性疾病和损伤的重要因素.
- 目前用于低通风的治疗方法往往具有局限性.
研究的目的:
- 调查中椎脊髓中DREADD表达是否可以刺激动力输出和隔膜激活.
- 为了确定焦点DREADD表达在性运动神经元中是否比非特异表达更有效.
- 评估这种方法是否能产生持续增加的启发性潮体积.
主要方法:
- 编码激发性DREADD (hM3D(Gq)) 的腺相关病毒 (AAV) 被注射到野生类型和ChAT-Cre小鼠的中椎脊髓 (C4).
- 在ChAT-Cre小鼠中,DREADD的表达被向的运动神经元,使用Cre依赖的病毒构造.
- 隔膜电肌图 (EMG) 和神经活动被记录.
- 整体体质谱被用来测量大鼠的潮体积.
- 为了激活DREADDs,使用了DREADD连接体JHU37160 (J60).
主要成果:
- 在两组小鼠中,JHU37160的使用导致了灵感EMG爆发的持续增加,而在ChAT-Cre小鼠中相对增加更大.
- 在老鼠中,JHU37160的给药导致了启发性潮体积的持续增加.
- 神经记录显示,JHU37160后的启发输出增加了200%以上.
结论:
- 将中椎脊柱DREADD表达向动神经元池的向允许带诱导的,持续增加动力输出和潮体积.
- 这种基于DREADD的方法具有临床应用的潜力,用于膜激活和低通风受损的条件.
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