In this study we examined the effect of BS on depression-like behavior in mice subjected to unpredictable chronic mild stress (UCMS) to clarify the antidepressant-like activity of BS and the molecular mechanism underlying this effect.
UCMS mice were administered BS daily (300 mg of dried herb weight/kg, p.o.) or a reference drug, imipramine (IMP, 10 mg/kg, i.p.), 1 week after starting the UCMS procedure. We employed the sucrose preference test and the tail suspension test to analyze anhedonia and depression- like behavior of mice, respectively. Serum and brain tissues of mice were used for neurochemical and immunohistochemical studies. The UCMS procedure induced anhedonia and depression-like behavior, and BS treatment, as well as IMP treatment, attenuated these symptoms.
UCMS caused an elevation of serum corticosterone level, an index of hyper-activation of the hypothalamic–pituitary–adrenal (HPA) axis, in a manner attenuated by BS and IMP treatment. BS treatment also attenuated UCMS-induced decrease in the expression levels of brain-derived neurotrophic factor (BDNF) mRNA, cyclic AMP- responsive element binding protein (CREB)and a phosphorylated form of N-methyl-D-aspartate receptor subunit NR1, synaptic plasticity-related signaling proteins. Moreover, the UCMS procedure reduced doublecortin-positive cells in the dentate gyrus region of the hippocampus. BS administration reversed these UCMS-induced neurochemical and histological abnormalities.
These results suggest that BS can ameliorate chronic stress-induced depression-like symptoms and that the effects of BS are mediated by restoring dysfunctions of the HPA axis and synaptic plasticity-related signaling systems and neurogenesis in the hippocampus.
Daishu Mizuki, Kinzo Matsumoto, Ken Tanaka, Xoan Thi Le, Hironori Fujiwara, Tsutomu Ishikawa, and Yoshihiro Higuchi
Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan
Graduate School of Pharmaceutical Sciences, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan
Material Development Laboratories, Shiratori Pharmaceutical Co.Ltd.,6-11-24 Tsudanuma, Narashino, Chiba 275-0016, Japan
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