Transcutaneous vagus nerve stimulation modulates depression‐like phenotype induced by high‐fat diet via P2X7R/NLRP3/IL‐1β in the prefrontal cortex

• DOI: 10.1111/cns.14755
• Publication Date: 2024-05-16T10:59:52Z
• Authors: Shaoyuan Li; Yuzhengheng Zhang; Yu Wang; Zixuan Zhang; Chen Xin; Yifei Wang; Peijing Rong
• Keywords: Vagus Nerve Stimulation

Abstract Background Depression is a common psychiatric disorder in diabetic patients. Depressive mood associated with obesity/metabolic disorders related to the inflammatory response caused by long‐term consumption of high‐fat diets, but its molecular mechanism unclear. In this study, we investigated whether antidepressant effect transcutaneous auricular vagus nerve stimulation (taVNS) diet rats works through P2X7R/NLRP3/IL‐1β pathway. Methods We first used 16S rRNA gene sequencing analysis and LC–MS metabolomics assays Zucker fatty (ZDF) (Purina #5008) induced significant depression‐like behaviors. Next, forced swimming test (FST) open field (OFT) were measured evaluate antidepressive taVNS. Immunofluorescence western blotting (WB) measure microglia state expression P2X7R, NLRP3, IL‐1β PFC. Results Purina#5008 behaviors ZDF was closely purine metabolites. Consecutive taVNS increased plasma insulin concentration, reduced glycated hemoglobin glucagon content rats, significantly improved depressive‐like phenotype reducing activity, prefrontal cortex (PFC). Conclusion The signaling pathway may play an important role antidepressant‐like behavior taVNS, which provides promising for clinical treatment diabetes combined depression.