Shimizu Shoko, Koyama Yoshihisa, Ishino Yugo, Takeda Takashi, Shimada Shoichi, Tohyama Masaya, Miyata Shingo
Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kindai University, Osaka-Sayama, JPN.
Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, Suita, JPN.
Cureus. 2024 Jun 30;16(6):e63526. doi: 10.7759/cureus.63526. eCollection 2024 Jun.
Kamishoyosan (KSS), a traditional Japanese Kampo medicine, is widely used to treat neuropsychiatric symptoms in perimenopausal and postmenopausal women. We aimed to elucidate the functional mechanisms underlying KSS-mediated reduction of stress response behaviors and neuropsychological symptoms in perimenopausal and postmenopausal women.
Female mice were bilaterally ovariectomized (OVX) at the age of 12 weeks and exposed to chronic water immersion and restraint stress for three weeks. Among them, mice in the OVX+stress+KSS group were fed chow containing KSS from one week before exposure to chronic stress until the end of the experiment. Firstly, we performed a marble burying test and measured serum corticosterone levels to assess irritability and stress conditions. Next, we examined whether KSS affects microRNA-18 (miR-18) and glucocorticoid receptor (GR) protein expression, as well as the basal dendritic spine morphology of pyramidal neurons in the medial prefrontal cortex (mPFC) of postmenopausal chronic stress-exposed mice. Analyzed data were expressed as mean ± standard deviation. Tukey's post hoc test, followed by analysis of variance (ANOVA), was used for among-group comparisons.
KSS administration normalized chronic stress-induced unstable emotion-like behavior and upregulated plasma corticosterone levels. Furthermore, KSS ameliorated GR protein expression by downregulating miR-18 expression in the mPFC and recovered the immature morphological changes in spine formation of pyramidal neurons in the mPFC of OVX mice following chronic stress exposure.
KSS administration in postmenopausal chronic stress-exposed mice exerted anti-stress effects and improved the basal dendritic spine morphology of pyramidal neurons by regulating miR-18 and glucocorticoid receptor expression in the mPFC.
加味逍遥散（KSS）是一种传统的日本汉方药物，广泛用于治疗围绝经期和绝经后女性的神经精神症状。我们旨在阐明KSS介导围绝经期和绝经后女性应激反应行为和神经心理症状减轻的功能机制。
12周龄雌性小鼠双侧卵巢切除（OVX），并暴露于慢性水浸和束缚应激3周。其中，OVX+应激+KSS组小鼠从暴露于慢性应激前1周开始喂食含KSS的饲料，直至实验结束。首先，我们进行了大理石埋藏试验并测量血清皮质酮水平，以评估易怒性和应激状态。接下来，我们研究KSS是否影响微小RNA-18（miR-18）和糖皮质激素受体（GR）蛋白表达，以及绝经后慢性应激暴露小鼠内侧前额叶皮质（mPFC）中锥体神经元的基底树突棘形态。分析数据以平均值±标准差表示。采用方差分析（ANOVA）后进行Tukey事后检验进行组间比较。
给予KSS可使慢性应激诱导的不稳定情绪样行为正常化，并上调血浆皮质酮水平。此外，KSS通过下调mPFC中miR-18的表达改善GR蛋白表达，并恢复慢性应激暴露后OVX小鼠mPFC中锥体神经元脊柱形成的未成熟形态变化。
在绝经后慢性应激暴露小鼠中给予KSS具有抗应激作用，并通过调节mPFC中miR-18和糖皮质激素受体表达改善锥体神经元的基底树突棘形态。
