Abstract
BackgroundStress-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 α7 nicotinic acetylcholine receptor (α7nAchR), and the hippocampus, the region with the most distribution of α7nAchR, regulates emotions. Here, we investigated the role of α7nAchR mediating hippocampal neuroinflammation in taVNS antidepressant effect though homozygous α7nAChR (−/−) gene knockout and α7nAchR antagonist (methyllycaconitine, MLA).MethodsThere were control, model, taVNS, α7nAChR(−/−) + 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 α7nAchR, NF-κB p65, IL-1β and the morphology of microglia were detected.ResultsDepression-like behavior and hippocampal neuroinflammation in CUMS model rats were manifested by down-regulated expression of α7nAchR, up-regulated expression of NF-κB p65 and IL-1β, 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 α7nAChR(−/−) rats and Hi MLA rats.ConclusionThe antidepressant effect of taVNS is related to hippocampal α7nAchR/NF-κB signal pathway.
Highlights
Stress-induced neuroinflammation was considered to play a critical role in the pathogenesis of depres‐ sion
Our previous results suggest that Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improved depression-like behavior and pain intensity as well as decreased the release of Tumor necrosis factor-α (TNF-α) in plasma, hypothalamus and hippocampus of the chronic unpredicted mild stress (CUMS) with chronic constriction injury of the sciatic nerve (CCI) model rats [21]
This study shows that the taVNS alleviates depressionlike behavior induced by CUMS in rats and is related to the α7 nicotinic acetylcholine receptor (α7nAchR)-mediated neuroinflammation in the hippocampus
Summary
Stress-induced neuroinflammation was considered to play a critical role in the pathogenesis of depres‐ sion. Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder. We investigated the role of α7nAchR mediating hippocampal neuroinflammation in taVNS antidepressant effect though homozygous α7nAChR (−/−) gene knockout and α7nAchR antagonist (methyllycaconi‐ tine, MLA). Major depressive disorder (MDD) is a highly prevalent mental health condition characterized by low mood, anhedonia, reduced energy, ruminative thoughts, impaired cognition, vegetative symptoms and suicidal attempts [1]. Epidemiological studies showed that the total estimated number of patients with depression worldwide is about 350 million, which is a leading cause of disability worldwide with a global prevalence of 2.6– 5.9% [2]. It is critical to develop more effective non-pharmaceutical treatment options including bioelectronic medicine
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