Anti‐neuroinflammation effects of transcutaneous auricular vagus nerve stimulation against depression‐like behaviors via hypothalamic α7nAchR/JAK2/STAT3/NF‐κB pathway in rats exposed to chronic unpredictable mild stress

• DOI: 10.1111/cns.14207
• Publication Date: 2023-04-10T07:24:53Z
• Authors: Yu Chen; Yue Zhang; Junying Wang; Shaoyuan Li; Yifei Wang; Zixuan Zhang; Jinling Zhang; Chen Xin; Yu Wang; Peijing Rong
• Keywords: Vagus Nerve Stimulation; Methyllycaconitine

Abstract Background Transcutaneous auricular vagus nerve stimulation (taVNS) is a vital neuromodulation for the treatment of depression, but its antidepressant molecular mechanism unclear. The α7 nicotinic acetylcholine receptor (α7nAchR) key mediator that mediates anti‐inflammatory efficacy. Here, we investigated whether effect taVNS in chronic unpredicted mild stress (CUMS)‐exposed rats works through α7nAchR/JAK2/STAT3/NF‐κB pathway. Methods depression model was established by CUMS continuous 6 weeks rats. From 4th week experiment, CUMS‐exposed were subjected to 3 weeks. To clarify role α7nAchR taVNS, used −/− gene knockout sucrose preference test (SPT), open field (OFT), and forced swimming (FST) evaluate depression‐like behaviors Immunofluorescent staining observe morphology microglia hypothalamus. Western blot examine protein expression α7nAchR, p‐JAK2, p‐STAT3, IL‐1β, NF‐κB p65, p‐NF‐κB p65 Results Depression‐like manifested decreased SPT ratio, increased FST immobility time, total distance, vertical movement score, activity time OFT. Hypothalamic neuroinflammation an amoebic‐like activated state microglia, downregulated upregulated IL‐1β. TaVNS could significantly reverse above‐mentioned phenomena, had poor improvement Conclusion hypothalamic signaling pathway may play important antidepressant‐like behavior taVNS.