Effects of intermittent theta-burst stimulation on depression-like behaviors and amino acid metabolism in the hippocampus of mice with chronic restraint stress
XUE Shanshan
ZHOU Cuihong
YU Huan
HAN Tianle
LI Mingyu
MA Xinxu
WANG Huaning
Abstract：Objective To investigate the effects of intermittent theta-burst stimulation(iTBS)on depression-like behaviors and hippocampal amino acid metabolism in a mouse model with chronic restraint stress(CRS).Methods Twenty-four male C57BL/6J mice aged 6-8 weeks were randomly divided into control group(Sham group),depression group(CRS group),and iTBS treatment group(CRS+iTBS group),with eight mice in each group.Following a week of adaptive feeding,mice in the CRS group and CRS+iTBS group underwent CRS modeling for 14 d.After modeling,the CRS+iTBS group received iTBS intervention for 5 d,while the Sham group and the CRS group underwent sham iTBS intervention for 5 d.Behavioral tests(sucrose preference test,novelty-suppressed feeding test,and tail suspension test)were conducted 24 h after iTBS intervention to evaluate depression-like behaviors.Subsequently,after 24 h of behavioral tests,the animals were sacrificed and hippocampal tissues from all groups were analyzed using untargeted metabolomics via ultra-high-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry(UHPLC-QTOF/MS)to assess alterations in amino acid metabolism.Results ①The results of sucrose preference test,novelty-suppressed feeding test,and tail suspension test among the three groups of mice were statistically significant(all P＜0.01).In the sucrose preference test,the CRS group exhibited a significantly lower sucrose preference rate compared to the Sham group and the CRS+iTBS group(both P＜0.01).In the novelty-suppressed feeding test,the feeding latency of mice in the CRS group was significantly higher than that in Sham group and CRS+iTBS group(both P＜0.01).In the tail suspension test,mice in the CRS group displayed a markedly longer immobility time compared to those in Sham group and CRS+iTBS group(both P＜0.01).②The results of UHPLC-QTOF/MS untargeted metabolomics analysis showed that a total of 119 amino acid metabolites were detected in the hippocampus of mice.Compared with the Sham group,there were 23 significantly down-regulated amino acid metabolites and 11 significantly up-regulated amino acid metabolites in the CRS group(both P＜0.05).Compared with the CRS group,a total of 19 significantly down-regulated amino acid metabolites and 1 significantly up-regulated amino acid metabolite were detected in the hippocampus of CRS+iTBS group after iTBS stimulation(P＜0.05).Conclusion iTBS can significantly improve depression-like behaviors in mice with CRS,and its regulatory effect on hippocampal amino acid metabolites may be one of its antidepressant mechanisms.
Keywords：major depressive disorderintermittent theta-burst stimulationhippocampusamino acid metabolism
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：7( 1613-1619 )