Galvanic vestibular stimulation-induced activation of C1 neurons in medulla oblongata protects against acute lung injury

Abstract

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 was 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 the GVS-induced protection against acute lung injury.

Hepatic glycogenolysis and hypometabolism induced by chemogenetic stimulation of C1 neurons

“…The present study showed that chemogenetic stimulation of C1 neurons decreased body temperature. A previous study from our laboratory demonstrated that hypergravity load‐induced hypothermia is partially blocked by selective deletion of C1 neurons (Abe et al., 2022, 2023). Furthermore, hypergravity load increases the expression of c‐fos in C1 neurons, and this response is significantly attenuated by peripheral vestibular lesions (Abe et al., 2019).…”

“…Moreover, photostimulation of C1 neurons decreases sympathetic nerve activity in brown adipose tissue through α 2 adrenergic receptors in the rostral raphe pallidus area (Madden et al., 2013). Furthermore, hypergravity load‐induced hypothermia was attenuated by selective deletion of C1 neurons (Abe et al., 2022). Accordingly, C1 neurons may participate in the regulation of metabolic states.…”