Chaihu-Shugan-San Administration Ameliorates Perimenopausal Anxiety and Depression in Rats

Abstract

Chaihu-Shugan-San (CSS) is a traditional Chinese herbal formula that is widely used for treating perimenopausal symptoms in China; however, its mechanisms remain unknown. The present study was designed to investigate potential CSS mechanisms in rats with unpredicted chronic mild stress (UCMS) and normally aging rats (52 weeks of age). We performed the sucrose consumption test along with the forced swimming test to confirm depression-like behavior and the open field test (OFT) to confirm anxiety-like behavior in the animals. In addition, we used an enzyme-linked immunosorbent assay to measure serum and hippocampal estradiol (E2) levels and a quantitative real-time polymerase chain reaction to assess hippocampal mRNA levels of estrogen receptors (ERs) α and β as well as G protein-coupled receptor 30 (GPR30). We found that CSS administration resulted in a significant increase in the ratio of hippocampal ERα and ERβ mRNA (ERα/ERβ ratio) in UCMS rats (p<0.001). However, no significant changes were observed in E2 levels, ERα mRNA expression, and GPR30 mRNA expression. In contrast, changes in ERα/ERβ mRNA ratio were sensitively associated with changes in mood states in the animal models. These findings suggest that enhancement of ERα/ERβ ratio may play a role in the pharmacological mechanisms of CSS. Furthermore, this ratio can be employed as a potential index for evaluating mood states in animal models and can be considered as a therapeutic target for perimenopausal anxiety and depression in the future.

Spontaneous failure of the estrous cycle induces anxiogenic-related behaviors in middle-aged female mice

“…As far as we are aware, only one study showed the effects of perimenopause on mood-related behaviors. Using a similar experimental design as herein presented, Chen et al [45] showed that middle-aged rats (52 weeks old) did not display any significant differences in the immobility time registered in the forced swimming test compared to young adult rats (20 weeks old). However, middle-aged female rats displayed anhedonic behaviors, which are a core symptom of depression, when subjected to chronic unpredictable stressful situations [45].…”

“…Using a similar experimental design as herein presented, Chen et al [45] showed that middle-aged rats (52 weeks old) did not display any significant differences in the immobility time registered in the forced swimming test compared to young adult rats (20 weeks old). However, middle-aged female rats displayed anhedonic behaviors, which are a core symptom of depression, when subjected to chronic unpredictable stressful situations [45]. These findings support the view that depressive-like behavior is possibly a common phenomenon sustained by prolonged low estrogen concentrations due to menopause and/or senescence.…”

The Role of Hippocampal Estradiol Receptor‐α in a Perimenopausal Affective Disorders‐Like Rat Model and Attenuating of Anxiety by Electroacupuncture

“…Seven different procedures were applied within six weeks. Each rat encountered one or two stresses per day, and the unexpectedness of the stress was guaranteed by the random onset of the procedures, which included broiling (40°C, 15 min), humidified cushion (12 h), cold water swimming (4°C, 5 min), noise (6 h), quaking (30 min), deprivation of food and water (12 h), and reversal of light and dark cycles according to the method that was explained by Chen et al [28]. …”

Brain-derived estrogen exerts anti-inflammatory and neuroprotective actions in the rat hippocampus

“…17β-estradiol levels in hippocampal CA1 tissue were measured using a sensitive ELISA method as described previously by others [39]. The 17β-Estradiol ELISA (ADI-900-174, Enzo Life Sciences, Farmingdale, NY) used in our studies has a detection range of 15.6–1000 pg/ml, and a sensitivity of 14.0 pg/ml.…”