Mechanisms underlying antidepressant effect of transcutaneous auricular vagus nerve stimulation on CUMS model rats based on hippocampal α7nAchR/NF-κB signal pathway

Background Stress-induced neuroinflammation was considered to play a critical role in the pathogenesis of depression. Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder. The anti-inflammatory signal of vagus nerve is mediated by alpha 7 nicotinic acetylcholine receptor (alpha 7nAchR), and the hippocampus, the region with the most distribution of alpha 7nAchR, regulates emotions. Here, we investigated the role of alpha 7nAchR mediating hippocampal neuroinflammation in taVNS antidepressant effect though homozygous alpha 7nAChR (-/-) gene knockout and alpha 7nAchR antagonist (methyllycaconitine, MLA). Methods There were control, model, taVNS, alpha 7nAChR(-/-) + taVNS, hippocampus (Hi) MLA + taVNS and Hi saline + taVNS groups. We used the chronic unpredicted mild stress (CUMS) method to establish depressive model rats for 42 days, excepting control group. After the successful modeling, except the control and model, the rats in the other groups were given taVNS, which was applied through an electroacupuncture apparatus at the auricular concha (2/15 Hz, 2 mA, 30 min/days) for 21 days. Behavioral tests were conducted at baseline, after modeling and after taVNS intervention, including sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST). These tests are widely used to evaluate depression-like behavior in rats. The samples were taken after experiment, the expressions of alpha 7nAchR, NF-kappa B p65, IL-1 beta and the morphology of microglia were detected. Results Depression-like behavior and hippocampal neuroinflammation in CUMS model rats were manifested by down-regulated expression of alpha 7nAchR, up-regulated expression of NF-kappa B p65 and IL-1 beta, and the morphology of microglia was in amoebic-like activated state. TaVNS could significantly reverse the above-mentioned phenomena, but had rare improvement effect for alpha 7nAChR(-/-) rats and Hi MLA rats. Conclusion The antidepressant effect of taVNS is related to hippocampal alpha 7nAchR/NF-kappa B signal pathway.

Automated summary

The anti-inflammatory signal of the vagus nerve mediated by alpha 7 nicotinic acetylcholine receptor (alpha 7nAchR) plays a critical role in the antidepressant effect of transcutaneous auricular vagus nerve stimulation (taVNS). The hippocampus region regulates emotions and has the most distribution of alpha 7nAchR, indicating its involvement in the taVNS antidepressant effect.