Bachmutsky Iris, Wei Xin Paul, Kish Eszter, Yackle Kevin
Department of Physiology, University of California-San Francisco, San Francisco, United States.
Neuroscience Graduate Program, University of California-San Francisco, San Francisco, United States.
Elife. 2020 Feb 19;9:e52694. doi: 10.7554/eLife.52694.
The rates of opioid overdose in the United States quadrupled between 1999 and 2017, reaching a staggering 130 deaths per day. This health epidemic demands innovative solutions that require uncovering the key brain areas and cell types mediating the cause of overdose- opioid-induced respiratory depression. Here, we identify two primary changes to murine breathing after administering opioids. These changes implicate the brainstem's breathing circuitry which we confirm by locally eliminating the µ-Opioid receptor. We find the critical brain site is the preBötzinger Complex, where the breathing rhythm originates, and use genetic tools to reveal that just 70-140 neurons in this region are responsible for its sensitivity to opioids. Future characterization of these neurons may lead to novel therapies that prevent respiratory depression while sparing analgesia.
1999年至2017年间，美国阿片类药物过量使用率增长了四倍，达到了惊人的每天130例死亡。这种健康危机需要创新解决方案，这就要求揭示介导过量使用阿片类药物导致呼吸抑制的关键脑区和细胞类型。在这里，我们确定了给小鼠使用阿片类药物后呼吸的两个主要变化。这些变化涉及脑干呼吸回路，我们通过局部消除μ-阿片受体来证实这一点。我们发现关键脑区是前包钦格复合体，呼吸节律起源于此，并使用基因工具揭示该区域仅70 - 140个神经元就决定了其对阿片类药物的敏感性。对这些神经元的进一步表征可能会带来新的治疗方法，既能预防呼吸抑制，又能保留镇痛效果。
