Optogenetic stimulation of the brainstem dorsal motor nucleus ameliorates acute pancreatitis.
Optogenetic stimulation of the brainstem dorsal motor nucleus ameliorates acute pancreatitis.
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DOI：
10.3389/fimmu.2023.1166212
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
炎症是一个固有的自我放大过程，如果不解决，会导致进行性组织损伤。这种正反馈系统的刹车是由神经系统提供的，神经系统已经进化到检测炎症信号并通过激活抗炎过程做出反应，包括由迷走神经介导的胆碱能抗炎途径。急性胰腺炎是一种常见且严重的疾病，没有有效的治疗，当腺泡细胞损伤激活胰腺内炎症时发生。先前的研究表明，电刺激颈动脉鞘（其中包含迷走神经）可增强内源性抗炎反应并改善急性胰腺炎，但尚不清楚这些抗炎信号是否源自大脑。在这里，我们使用光遗传学选择性激活源自脑干迷走神经背运动核（DMN）的输出神经纤维，并评估其对小蛋白诱导的胰腺炎的影响。通过降低血清淀粉酶、胰腺细胞因子、组织损伤和水肿，刺激DMN中的胆碱能神经元可显著减轻胰腺炎的严重程度。无论是迷走神经切断术还是通过预先施用拮抗剂甲胺来沉默胆碱能烟碱受体信号都会消除有益的效果。这些结果首次证明，脑干DMN中的传出迷走神经胆碱能神经元可以抑制胰腺炎症，并暗示胆碱能抗炎途径是急性胰腺炎的潜在治疗靶点。
Inflammation is an inherently self-amplifying process, resulting in progressive tissue damage when unresolved. A brake on this positive feedback system is provided by the nervous system which has evolved to detect inflammatory signals and respond by activating anti-inflammatory processes, including the cholinergic anti-inflammatory pathway mediated by the vagus nerve. Acute pancreatitis, a common and serious condition without effective therapy, develops when acinar cell injury activates intrapancreatic inflammation. Prior study has shown that electrical stimulation of the carotid sheath, which contains the vagus nerve, boosts the endogenous anti-inflammatory response and ameliorates acute pancreatitis, but it remains unknown whether these anti-inflammatory signals originate in the brain. Here, we used optogenetics to selectively activate efferent vagus nerve fibers originating in the brainstem dorsal motor nucleus of the vagus (DMN) and evaluated the effects on caerulein-induced pancreatitis. Stimulation of the cholinergic neurons in the DMN significantly attenuates the severity of pancreatitis as indicated by reduced serum amylase, pancreatic cytokines, tissue damage, and edema. Either vagotomy or silencing cholinergic nicotinic receptor signaling by pre-administration of the antagonist mecamylamine abolishes the beneficial effects. These results provide the first evidence that efferent vagus cholinergic neurons residing in the brainstem DMN can inhibit pancreatic inflammation and implicate the cholinergic anti-inflammatory pathway as a potential therapeutic target for acute pancreatitis.
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影响因子：
4.6
作者：
Fontaine AK;Ramirez DG;Littich SF;Piscopio RA;Kravets V;Schleicher WE;Mizoguchi N;Caldwell JH;Weir RFF;Benninger RKP
通讯作者：
Benninger RKP
影响因子：
29.4
作者：
Gukovskaya AS;Gukovsky I;Algül H;Habtezion A
通讯作者：
Habtezion A
迷走神经的选择性神经调节。
影响因子：
4.3
作者：
Fitchett A;Mastitskaya S;Aristovich K
通讯作者：
Aristovich K
影响因子：
3
作者：
Jacob, Tony G.;Raghav, Rahul;Roy, Tara S.
通讯作者：
Roy, Tara S.
影响因子：
3.1
作者：
BACK, N;AHONEN, M;KIVILUOTO, T
通讯作者：
KIVILUOTO, T