Modified Xiaoyaosan reverses aberrant brain regional homogeneity to exert antidepressive effects in mice

Abstract

The aim of this study is to explore the macroscale neural mechanisms of the antidepressant effects of Xiaoyaosan, a traditional Chinese herbal formula. We analyzed blood oxygen level‐dependent (BOLD) functional magnetic resonance imaging signals. To further minimize the hemodynamic variations of BOLD signals and analyze the intra‐region neural activity or temporal coherence, we employed the newly developed regional homogeneity (ReHo) approach to determine aberrant functional connectivity using the chronic unpredictable mild stress (CUMS) mouse model of depression and to also explore the brain‐region rescue effect of modified Xiaoyaosan (MXYS) in such mice. We found the aberrant ReHo in CUMS mice replicated previous discoveries in patients with depression. Intriguingly, MXYS only normalized several limbic regions, which suggests the essential roles of these regions in mediating the antidepressant effects of MXYS. Our results provide a reliable framework for the use of ReHo analysis with animal models of depression and further suggest a new perspective to elucidate the antidepressant effects of MXYS.

Xiaoyaosan Exerts Antidepressant Effect by Downregulating RAGE Expression in Cingulate Gyrus of Depressive-Like Mice

“…In MDD patients, the function of anterior and posterior Cg was low and blood flow metabolism was abnormal ( Videbech, 2000 ; Qiu et al, 2020 ). Modified Xiaoyaosan reversed the ReHo value in some abnormal brain areas of CUMS mice ( Bi et al, 2019 ) and corrected the BOLD signal function and the hippocampal nerve function ( Gao et al, 2018 ). Interestingly, using the Cg as the seed point analysis, we found that both interhemisphereric and intrahemispheric FC decreased in chronic stress–induced depressive-like mice, which was consistent with the results of clinical MDD reports ( Yang et al, 2016 ; Qiu et al, 2020 ).…”