Identification of a brainstem locus that inhibits tumor necrosis factor.
Identification of a brainstem locus that inhibits tumor necrosis factor.
复制标题
DOI：
10.1073/pnas.2008213117
复制
发表时间：
2020-11-24
影响因子：
11.1
通讯作者：
Tracey KJ
中科院分区：
文献类型：
--
作者：
Kressel AM;Tsaava T;Levine YA;Chang EH;Addorisio ME;Chang Q;Burbach BJ;Carnevale D;Lembo G;Zador AM;Andersson U;Pavlov VA;Chavan SS;Tracey KJ
由于迷走神经信号抑制炎症和细胞因子的产生，刺激迷走神经电活动的电子装置正在研究用于类风湿性关节炎、炎性肠病和其他炎性综合征的临床用途。迷走神经机制，称为炎症反射，已被广泛研究，但控制炎症的迷走神经纤维的起源和功能性神经解剖学以前是未知的。在这里，我们揭示了胆碱能神经元在脑干背侧运动核（DMN）的迷走神经投射到腹腔肠系膜上神经节和传输抑制信号的脾神经。通过结合光遗传学、解剖和功能映射以及TNF产生的测量，我们的数据显示DMN是控制炎症反射中抗炎信号的重要脑干位点。在大脑中，紧凑的神经元细胞体簇（称为细胞核）对于将宿主生理参数维持在最佳健康范围内至关重要。位于脑干背侧运动核（DMN）中的神经元在迷走神经中投射以与肺、肝、胃肠道和其他器官通信。迷走神经介导的反射还通过抑制脾脏中肿瘤坏死因子（TNF）和其他细胞因子的产生来控制免疫系统对感染和损伤的反应，尽管DMN神经元在调节TNF释放中的功能尚不清楚。在这里，光遗传学和功能定位揭示了DMN中的胆碱能神经元，其投射到腹腔-肠系膜上神经节，显著增加脾神经活性并抑制TNF产生。终止于腹腔-肠系膜上神经节的传出迷走神经纤维形成静脉曲张样结构，围绕支配脾脏的单个神经细胞体。DMN胆碱能神经元的选择性光遗传激活或颈迷走神经的电激活在脾神经中引起动作电位。迷走神经的药物阻断和手术切断抑制迷走神经诱发的脾神经反应。这些结果表明，位于脑干DMN的胆碱能神经元控制TNF的产生，揭示了脑干免疫协调的作用。
Electronic devices that stimulate electrical activity in the vagus nerve are being studied for clinical use in rheumatoid arthritis, inflammatory bowel disease, and other inflammatory syndromes because vagus nerve signals inhibit inflammation and cytokine production. A vagus nerve mechanism, termed the inflammatory reflex, has been widely studied, but the origin and functional neuroanatomy of vagus nerve fibers controlling inflammation were previously unknown. Here we reveal cholinergic neurons in the brainstem dorsal motor nucleus (DMN) of the vagus projecting to the celiac-superior mesenteric ganglia and transmitting cytokine-inhibiting signals to the splenic nerve. By combining optogenetics, anatomical and functional mapping, and measurement of TNF production, our data show the DMN is an important brainstem locus controlling anti-inflammatory signals in the inflammatory reflex. In the brain, compact clusters of neuron cell bodies, termed nuclei, are essential for maintaining parameters of host physiology within a narrow range optimal for health. Neurons residing in the brainstem dorsal motor nucleus (DMN) project in the vagus nerve to communicate with the lungs, liver, gastrointestinal tract, and other organs. Vagus nerve-mediated reflexes also control immune system responses to infection and injury by inhibiting the production of tumor necrosis factor (TNF) and other cytokines in the spleen, although the function of DMN neurons in regulating TNF release is not known. Here, optogenetics and functional mapping reveal cholinergic neurons in the DMN, which project to the celiac-superior mesenteric ganglia, significantly increase splenic nerve activity and inhibit TNF production. Efferent vagus nerve fibers terminating in the celiac-superior mesenteric ganglia form varicose-like structures surrounding individual nerve cell bodies innervating the spleen. Selective optogenetic activation of DMN cholinergic neurons or electrical activation of the cervical vagus nerve evokes action potentials in the splenic nerve. Pharmacological blockade and surgical transection of the vagus nerve inhibit vagus nerve-evoked splenic nerve responses. These results indicate that cholinergic neurons residing in the brainstem DMN control TNF production, revealing a role for brainstem coordination of immunity.
登录
查看更多内容
影响因子：
2.7
作者：
Borovikova, LV;Ivanova, S;Tracey, KJ
通讯作者：
Tracey, KJ
影响因子：
3.5
作者：
Bonaz, B.;Sinniger, V.;Pellissier, S.
通讯作者：
Pellissier, S.
影响因子：
25
作者：
Boyden, ES;Zhang, F;Deisseroth, K
通讯作者：
Deisseroth, K
影响因子：
3.7
作者：
Levine YA;Koopman FA;Faltys M;Caravaca A;Bendele A;Zitnik R;Vervoordeldonk MJ;Tak PP
通讯作者：
Tak PP
DOI：
10.4049/jimmunol.1601613
发表时间：
2017-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chavan SS;Tracey KJ
通讯作者：
Tracey KJ