Abe Chikara, Katayama Chikako, Ohbayashi Kento, Horii Kazuhiro, Ogawa Bakushi, Fujimoto Chisato, Iwasaki Yusaku, Nin Fumiaki, Morita Hironobu
Department of Physiology, Gifu University Graduate School of Medicine, Gifu, Japan.
Preemptive Food Research Center (PFRC), Gifu University Institute for Advanced Study, Gifu, Japan.
Am J Physiol Regul Integr Comp Physiol. 2023 Feb 1;324(2):R152-R160. doi: 10.1152/ajpregu.00131.2022. Epub 2022 Dec 19.
Autonomic nerves, including the sympathetic and parasympathetic nerves, control the immune system along with their physiological functions. On the peripheral side, the interaction between the splenic sympathetic nerves and immune cells is important for the anti-inflammatory effects. However, the central mechanism underlying these anti-inflammatory effects remains unclear. C1 neurons respond to stressors and subsequently determine the outflow of the autonomic nervous system. We have previously shown that C1 neurons protect against acute kidney injury and found a signaling connection between peripheral vestibular organs and C1 neurons. Thus, we hypothesized that hypergravity load or galvanic vestibular stimulation (GVS) might protect against acute lung injury. We showed that C1 neurons are histologically and functionally activated by stimulating the peripheral vestibular organs. Protection against acute lung injury that was induced by a 2 G load disappeared due to vestibular lesions or the deletion of C1 neurons. This GVS-induced protective effect was also eliminated by the deletion of the C1 neurons. Furthermore, GVS increased splenic sympathetic nerve activity in conscious mice, and splenic sympathetic denervation abolished the GVS-induced protection against acute lung injury. Therefore, the activated pathway between C1 neurons and splenic sympathetic nerves is indispensable for GVS-induced protection against acute lung injury.
自主神经，包括交感神经和副交感神经，在控制免疫系统的同时也执行其生理功能。在外周，脾交感神经与免疫细胞之间的相互作用对于抗炎作用至关重要。然而，这些抗炎作用的中枢机制仍不清楚。C1神经元对应激源作出反应，并随后决定自主神经系统的输出。我们之前已经表明C1神经元可预防急性肾损伤，并发现外周前庭器官与C1神经元之间存在信号连接。因此，我们推测高重力负荷或电刺激前庭（GVS）可能预防急性肺损伤。我们发现，刺激外周前庭器官可在组织学和功能上激活C1神经元。由于前庭损伤或C1神经元缺失，由2G负荷诱导的急性肺损伤的保护作用消失。C1神经元缺失也消除了GVS诱导的保护作用。此外，GVS增加了清醒小鼠的脾交感神经活动，而脾交感神经去神经支配消除了GVS诱导的对急性肺损伤的保护作用。因此，C1神经元与脾交感神经之间的激活通路对于GVS诱导的急性肺损伤保护作用不可或缺。
