Transcutaneous Auricular Vagus Stimulation Attenuates LPS-Induced Depression-like Behavior by Regulating Central α7nAChR/JAK2 Signaling

Abstract

Depression is a serious disabling disease worldwide. Accumulating evidence supports that there is a close relationship between depression and inflammation, then inhibition of neuroinflammation may be another mechanism for the treatment of depression. Transcutaneous Auricular Vagus Stimulation(taVNS), as a non-invasive transcutaneous electrical stimulation, could effectively treat depression, but its mechanism is unclear. In this study, rats with depression-like behavior were induced by intraperitoneal injection of lipopolysaccharide (LPS). The rats were randomly divided to Control group, LPS group, taVNS + LPS group and the same as the α7 nicotinic acetylcholine chloride receptor(α7nAChR) (-/-) gene knockout rats. The expressions of tumor necrosis factor-alpha (TNF-ɑ) and phosphorylated-Janus kinase2(p-JAK2),phosphorylated-signal transducer and activator of transcription3(p-STAT3) in the hypothalamus, amygdala and hippocampus were detected by Western Blot. We observed that LPS significantly decreased the sucrose preference, the time of into the open arms in the elevated plus maze, and the number of corssing and reaing in the open field test. TaVNS treatment improves these depression-like behaviors, but taVNS is not effective in α7nAChR (-/-) gene knockout rats. The expression of TNF-ɑ signifciantly increased, and the expression of p-Jak2 and p-STAT3 markedly decreased in the hypothalamus and amygdala induced by LPS. TaVNS could significantly reverse the above-mentioned phenomena but had rare improvement effect for α7nAChR(-/-) rats. We conclude that the antidepressant effect of taVNS for LPS-induced depressive rats is related to α7nAchR/JAK2 signal pathway in the hypothalamus and amygdala.