Hippocampal activation of 5‐HT_1B receptors and BDNF production by vagus nerve stimulation in rats under chronic restraint stress

Abstract

A growing body of evidence shows that the electrical stimulation of the vagus nerve can improve mental illness including depression. Here, we investigated whether the vagus nerve stimulation (VNS) is involved in regulating the responsiveness of hippocampal neurons in rats under chronic restraint stress (CRS). c‐Fos protein signals were detected 2 hr after VNS in 5‐HT1A receptor‐positive neurons in the dorsal raphe nucleus (DRN) as well as in the nucleus tractus solitarius (NTS). Chronic VNS was performed on a daily basis for 2 weeks using an implanted microelectrode in rats that had undergone CRS for 2 weeks. We found that the levels of both 5‐HT1B receptors and phospho‐Erk1/2 were decreased in parallel in the hippocampal neurons of CRS animals and then increased to the baseline levels by chronic VNS. Hippocampal induction of 5‐HT1B receptors and phospho‐Erk1/2 by VNS was diminished after the injection of 5,7‐dihydroxytryptamine (5,7‐DHT), a neurotoxin of serotonergic neurons, into the DRN. Hippocampal production of brain‐derived neurotrophic factor (BDNF) was also upregulated by VNS, but the treatment of 5,7‐DHT abrogated the effects of VNS on BDNF induction. VNS in CRS animals improved the behavioral scores in forced swimming test (FST) compared to sham‐stimulated control. Our results suggest that VNS‐mediated serotonergic input via 5‐HT1B receptors into the hippocampal neurons may activate BDNF pathway and improve depressive‐like behaviors in CRS animals.

Acupuncture stimulation attenuates TNF-α production via vagal modulation in the concanavalin A model of hepatitis

“…We have previously demonstrated that sham needle stimulation around ST36 can partially induce acupuncture-like responses such as the induction of α6 integrin at the stimulation site or increased expression of GAP-43 and Erk1/2 in the dorsal root ganglion (DRG). 15,30 Transcutaneous electrical stimulation and EA show similar effectiveness in the regulation of gastric motility in humans. 31 We therefore speculate that acupuncture needle stimulation may have varying anti-inflammatory effects depending on subcutaneous locations (i.e.…”

“…Electrical current (10 mA, 5 Hz, pulse duration: 5 ms, A-M Systems) was delivered for 5 min, as described in our previous report. 15…”

Vagal afferent fibers contribute to the anti-inflammatory reactions by vagus nerve stimulation in concanavalin A model of hepatitis in rats

“…The electrical current (10 mA, 5 Hz, 5 ms of pulse duration, 5 min) was applied by using the isolated pulse stimulator (model 2100, A-M Systems Inc., Sequim, WA, USA). Our previous study showed that the same stimulation protocol for the acute and chronic VNS at the cervical level was effective to induce the activation of neurons in the dorsal raphe nucleus and the hippocampal neurons in rats (Shin et al 2019). After hVNS, the abdomen was closed by 5-0 nylon suture, and animals were returned to animal room and sacrificed 1-3 days later.…”

Vagal Afferent Fibers Contribute to the Anti-Inflammatory Reactions by Vagus Nerve Stimulation in Concanavalin A Model of Hepatitis in Rats

“…Exposed nerve was placed in a bipolar hook electrode of nichrome wire, and the electrical current (10 mA, 5 Hz, 5 ms of pulse duration, 5 min) was applied by using the isolated pulse stimulator (model 2100, A-M Systems Inc., Sequim, WA, USA). We used this stimulation condition based on our previous study showing an e cient induction of AFVN leading to activation of hippocampal neurons (Shin et al 2019). After hVNS, animals were returned to animal room and sacri ced 1 -3 days later.…”