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Neuropathology. 2019 Apr;39(2):85-96. doi: 10.1111/neup.12540. Epub 2019 Mar 4.

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

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School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
Foshan Maternal and Child Health Research Institute, Affiliated Hospital of Southern Medical University, Foshan, China.
School of Nursing, Guangzhou University of Chinese Medicine, Guangzhou, China.
The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.


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.


MXYS; depression; fMRI; hippocampus; regional homogeneity

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