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
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DOI：
10.1097/ccm.0000000000002646
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Xiangming Fang
中科院分区：
文献类型：
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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
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)
