Role of hippocampal neurometabolites in the antidepressant mechanism of iTBS based on non-targeted metabolomics
XUE Shanshan
CHEN Dongyu
CAI Yanhui
WANG Huaning
HAN Tianle
Abstract：Objective To investigate the effects of intermittent theta-burst stimulation(iTBS)on hippocampal neurometabolites in depression-like mouse model induced by chronic restraint stress(CRS)to elucidate its antidepressant mechanisms.Methods A depression-like mouse model of CRS was constructed,and mice meeting the modeling criteria were randomly divided into true stimulation group(CRS+iTBS group,n=8)and pseudo-stimulation group(CRS group,n=8).Following 5 d of iTBS treatment,the therapeutic efficacy was assessed via sucrose preference test and tail suspension test.Non-targeted metabolomics based on ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry was used to detect hippocampal neurometabolites,and orthogonal partial least squares discriminant analysis and variable importance in projection were used to screen key metabolites.Results iTBS significantly ameliorated depressive-like behaviors in CRS+iTBS group(P＜0.05),and non-targeted metabolomics revealed three neurometabolites with significant differences(P＜0.05).Leukotriene C4(LTC4)demonstrated the most pronounced alterations:LTC4 levels were significantly elevated in the hippocampus of CRS mice compared to those of the control group(P＜0.01),while iTBS intervention partially reversed this dysregulation(P＜0.01).Conclusion Hippocampal LTC4 may be one of the critical molecules mediating the antidepressant effects of iTBS.
Keywords：major depressive disorderintermittent theta-burst stimulationhippocampusneurometaboliteleukotrienenon-targeted metabolomics
Publication Date：2025-12-31
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：5( 1620-1624 )