国内团队Cell：破解“恶心-呕吐”反应的肠脑轴神经机制
- ①开发一个小鼠实验范式，研究细菌肠毒素如何引起恶心（味觉回避）和呕吐（干呕）防御反应；
- ②鉴定出传递毒素相关信号的肠-脑轴神经环路：表达5-羟色胺（5-HT）的肠嗜铬细胞→表达5-HT受体（Htr3a）的迷走神经元→背迷走神经复合体（DVC）的Tac1+神经元；
- ③Tac1+ DVC神经元通过分别激活脑桥臂旁外侧核（LPB）和延髓呼吸中枢（rVRG），来引发厌恶情绪和干呕行为；
- ④Tac1+ DVC神经元也介导化疗药物引起的恶心和呕吐行为；
- ⑤肠道的免疫-神经内分泌轴或参与毒素感知。
主编推荐语
摄入被毒素污染的食物后，大脑会启动恶心、干呕和呕吐等一系列的防御反应。大脑如何察觉摄入的毒素并协调不同的防御反应，其背后的机制尚不清楚。北京生命科学研究所的曹鹏团队在Cell发表最新研究，在小鼠中鉴定出细菌肠毒素和化疗药物引起的“恶心-呕吐”反应的肠-脑轴神经机制。
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The gut-to-brain axis for toxin-induced defensive responses
参与毒素诱导的防御反应的肠-脑轴
10.1016/j.cell.2022.10.001
2022-11-01, Article
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After ingestion of toxin-contaminated food, the brain initiates a series of defensive responses (e.g., nausea, retching, and vomiting). How the brain detects ingested toxin and coordinates diverse defensive responses remains poorly understood. Here, we developed a mouse-based paradigm to study defensive responses induced by bacterial toxins. Using this paradigm, we identified a set of molecularly defined gut-to-brain and brain circuits that jointly mediate toxin-induced defensive responses. The gut-to-brain circuit consists of a subset of Htr3a+ vagal sensory neurons that transmit toxin-related signals from intestinal enterochromaffin cells to Tac1+ neurons in the dorsal vagal complex (DVC). Tac1+ DVC neurons drive retching-like behavior and conditioned flavor avoidance via divergent projections to the rostral ventral respiratory group and lateral parabrachial nucleus, respectively. Manipulating these circuits also interferes with defensive responses induced by the chemotherapeutic drug doxorubicin. These results suggest that food poisoning and chemotherapy recruit similar circuit modules to initiate defensive responses.
First Authors:
Zhiyong Xie,Xianying Zhang,Miao Zhao,Lifang Huo
Correspondence Authors:
Zhiyong Xie,Fengchao Wang,Congping Shang,Peng Cao
All Authors:
Zhiyong Xie,Xianying Zhang,Miao Zhao,Lifang Huo,Meizhu Huang,Dapeng Li,Shuangfeng Zhang,Xinyu Cheng,Huating Gu,Chen Zhang,Cheng Zhan,Fengchao Wang,Congping Shang,Peng Cao
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