Selective Activation of Basal Forebrain Cholinergic Neurons Attenuates Polymicrobial Sepsis–Induced Inflammation via the Cholinergic Anti-Inflammatory Pathway
Selective Activation of Basal Forebrain Cholinergic Neurons Attenuates Polymicrobial Sepsis–Induced Inflammation via the Cholinergic Anti-Inflammatory Pathway
复制标题
选择性激活基底前脑胆碱能神经元可通过胆碱能抗炎途径减轻多种微生物脓毒症引起的炎症
DOI：
10.1097/ccm.0000000000002646
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Xiangming Fang
中科院分区：
文献类型：
--
作者：
Qian Zhai;Dengming Lai;Ping Cui;Rui Zhou;Qixing Chen;Jinchao Hou;Yunting Su;Libiao Pan;Hui Ye;Jing-Wei Zhao;Xiangming Fang
干预措施：基础前脑的胆碱能神经元活性是在光遗传学上进行的。血清和脾脏中的因子-α和白介素-6在光验证的聊天小鼠中，结扎和穿刺与左宫颈迷走神经结合，这些减少的肿瘤坏死因子-α和白介素6的降低是部分反向的％为Tyro-Sine羟化酶阳性神经元。此外，化学否认表明，对脾脏的多巴胺能神经递质对于抗炎是必不可少的。结论：这些结果是第一个在选择性激活基本的前脑胆碱能神经元足以衰减的基本炎症的基础上，sepsis sepsis cortimin cortimin cortimin cortimin cortimin cortimin cortimin cortimin cortimin cortimin cortimin cortimitive cortimin cortimitivemin。固体核的迷走神经/腹侧部分背运动核中的ur龙，这种多巴胺能有效信号通过迷走神经进一步传播到每个胆碱能神经元到周围器官。
Interventions: The cholinergic neuronal activity of the basal fore-brain was manipulated optogenetically. Cecal ligation and punc-ture was produced to induce sepsis. Left cervical vagotomy and 6-hydroxydopamine injection to the spleen were used. Measurements and Main Results: Photostimulation of basal fore-brain cholinergic neurons induced a significant decrease in the levels of tumor necrosis factor-α and interleukin-6 in the serum and spleen. When cecal ligation and puncture was combined with left cervical vagotomy in photostimulated ChAT mice, these reductions in tumor necrosis factor-α and interleukin-6 were partly reversed. Furthermore, photostimulating basal forebrain choliner-gic neurons induced a large increase in c-Fos expression in the basal forebrain, the dorsal motor nucleus of the vagus, and the ventral part of the solitary nucleus. Among them, 35.2% were tyro-sine hydroxylase positive neurons. Furthermore, chemical dener-vation showed that dopaminergic neurotransmission to the spleen is indispensable for the anti-inflammation..Conclusions: These results are the first to demonstrate that selec-tively activating basal forebrain cholinergic neurons is sufficient to attenuate systemic inflammation in sepsis. Specifically, photostimu-lation of basal forebrain cholinergic neurons activated dopaminer-gic neurons in dorsal motor nucleus of the vagus/ventral part of the solitary nucleus, and this dopaminergic efferent signal was further transmitted by the vagus nerve to the spleen. This cholinergic-to-dopaminergic neural circuitry, connecting central cholinergic neurons to the peripheral organ, might have mediated the anti-inflammatory effect in sepsis. (Crit Care Med 2017; 45:e1075–e1082)
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影响因子：
16.6
作者：
Anaclet C;Pedersen NP;Ferrari LL;Venner A;Bass CE;Arrigoni E;Fuller PM
通讯作者：
Fuller PM
影响因子：
5.3
作者：
Ma, Ming;Luo, Minmin
通讯作者：
Luo, Minmin
影响因子：
16.2
作者：
Conner, JM;Chiba, AA;Tuszynski, MH
通讯作者：
Tuszynski, MH
DOI：
10.1523/jneurosci.4432-14.2015
发表时间：
2015-02
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
David Tingley;A. Alexander;L. Quinn;A. Chiba;D. Nitz
通讯作者：
David Tingley;A. Alexander;L. Quinn;A. Chiba;D. Nitz
影响因子：
2.3
作者：
Kessler, W;Traeger, T;Heidecke, CD
通讯作者：
Heidecke, CD