Effects of Radix Polygalae on Cognitive Decline and Depression in Estradiol Depletion Mouse Model of Menopause

Postmenopausal syndrome refers to symptoms caused by the gradual decrease in female hormones after mid-40 years. As a target organ of estrogen, decrease in estrogen causes various changes in brain function such as a decrease in choline acetyltransferase and brain-derived neurotrophic factor; thus, postmenopausal women experience cognitive decline and more depressive symptoms than age-matched men. Radix Polygalae has been used for memory boosting and as a mood stabilizer and its components have shown neuroprotective, antidepressant, and stress relief properties. In a mouse model of estrogen depletion induced by 4-vinylcyclohexene diepoxide, Radix Polygalae was orally administered for 3 weeks. In these animals, cognitive and depression-related behaviors and molecular changes related to these behaviors were measured in the prefrontal cortex and hippocampus. Radix Polygalae improved working memory and contextual memory and despair-related behaviors in 4-vinylcyclohexene diepoxide-treated mice without increasing serum estradiol levels in this model. In relation to these behaviors, choline acetyltransferase and brain-derived neurotrophic factor in the prefrontal cortex and hippocampus and bcl-2-associated athanogene expression increased in the hippocampus. These results implicate the possible benefit of Radix Polygalae in use as a supplement of estrogen to prevent conditions such as postmenopausal depression and cognitive decline.

A Detailed Biological Approach on Hormonal Imbalance Causing Depression in Critical Periods (Postpartum, Postmenopausal and Perimenopausal Depression) in Adult Women

Background: In today's global world, most women are experiencing midlife health problems which can affect their lives and mental status. Most of the diseases occurr after childbirth and during pregnancy or gestation period which can lead to severe problems such as postpartum depression (PPD), postmenopausal depression, perimenopausal depression which ultimately affects the mental health condition and develop various depressive episodes which ultimately lead to depression in women. Objective: The review paper gives the information that if there is untreated maternal depression then it can lead to anxiety, fear, negative effect on child development, disruption of the mother-infant relationship, and the occurrence of depressive symptoms in the early life of infants. Hormone levels are changed at the time of pregnancy. Methods: The data was collected by studying combination of research and review papers from different databases like PubMed, Medline, and Web of science by using search keywords like “Postpartum depression”, “Postmenopausal depression”, “Risk factors”, “Pathogenesis of PPD”, “Predictors of postpartum depression”. Results: This can lead to disrupting the quality of life of menopausal women like deficiency of nutrients, not properly regular physical activities, elevated Body Mass Index (BMI), loss of libido (loss of interest in sexual activities), due to the lack of education, and awareness among the people. Factors like increase in physical activity can naturally help in PPD condition. Mind body therapy, drug therapy and cognitive and mindfulness-based therapies help in hormonal imbalances. Conclusion: It was found that low birth weight and congenital abnormalities in babies lead to affect depression after delivery. It is recommended that health care providers and physicians are provided with information regarding factors contributing PPD and postmenopausal depression. Sleep timings and consumptions of nutraceuticals can help in natural healing with depression amongst women suffering from postpartum, postmenopausal and perimenopausal depression.

Antidepressive Effects of Kamishoyosan through 5-HT1AReceptor and PKA-CREB-BDNF Signaling in the Hippocampus in Postmenopausal Depression-Model Mice

Females are well known to suffer disproportionately more than males from stress-related neuropsychiatric disorders, especially during perimenopausal and postmenopausal periods. In addition to a decline in serum estradiol levels, environmental stress and social stress likely contribute to the development of neuropsychiatric symptoms in perimenopausal and postmenopausal women. Kamishoyosan (KSS) is a traditional Japanese Kampo medicine, composed of a specified mixture of 10 crude compounds derived from plant sources, widely used for various neuropsychiatric symptoms in perimenopausal and postmenopausal women. However, the molecular mechanisms underlying KSS-mediated attenuation of neuropsychological symptoms and stress-response behaviors in perimenopausal and postmenopausal women remain unknown. In the present study, we first established a mouse model for postmenopausal depression-like signs using chronic water-immersion and restraint-stressed ovariectomized (OVX) mice to investigate the underlying molecular mechanism of KSS. We found that continuous administration of KSS to these mice normalized the activation of the hypothalamic-pituitary-adrenal (HPA) axis, ameliorated stress-induced depressive behavior, and prevented a decrease of neurogenesis in the hippocampus. As previous studies have implicated dysfunction of the hippocampal 5-HT1A receptor (5-HT1AR) in depressive disorders, we also evaluated the effect of KSS on 5-HT1AR expression and the protein kinase A- (PKA-) cAMP response element-binding- (CREB-) brain-derived neurotrophic factor (BDNF) signaling pathway in the hippocampus in this model. The level of 5-HT1AR in the hippocampus decreased in chronic stress-exposed OVX mice, while KSS treatment normalized the stress-induced decrease in 5-HT1AR expression in the hippocampus of chronic stress-exposed OVX mice. Furthermore, we found that KSS treatment upregulated the expression levels of phosphorylated PKA (p-PKA), phosphorylated CREB (p-CREB), and BDNF in the hippocampus in chronic stress-exposed OVX mice. These results suggest that KSS improves neuropsychiatric symptoms through 5-HT1AR and PKA-CREB-BDNF signaling in the hippocampus in postmenopausal women.

MicroRNA-99a is a Potential Target for Regulating Hypothalamic Synaptic Plasticity in the Peri/Postmenopausal Depression Model

Accumulating evidence has demonstrated that there is a growing trend of menopausal women suffering from depression. However, the pathogenesis of menopausal depression still remains unclear. Hence, this paper aims to reveal the pathological mechanisms involved in postmenopausal depression by using a novel peri- to postmenopausal depression model induced by a two-step ovariectomy plus chronic mild stress (CMS). The results of metabolic chambers and serum hormone/cytokine determination revealed that peri/postmenopausal depressive mice exhibited endocrine and metabolic disorders. Electrophysiological recordings indicated that the hippocampal synaptic transmission was compromised. Compared to the sham group, the microRNA-99a (miR-99a) level decreased significantly in the hypothalamus, and its target FK506-binding protein 51 (FKBP51) enormously increased; in contrast, the nuclear translocation of the progesterone receptor (PR) decreased in hypothalamic paraventricular nucleus (PVN) in the peri/postmenopausal depression mouse model. Additionally, synaptic proteins, including postsynaptic density protein 95 (PSD-95) and synaptophysin (SYN), showed a similar decrease in the hypothalamus. Accordingly, the present work suggests that miR-99a may be involved in the regulation of hypothalamic synaptic plasticity and that it might be a potential therapeutic target for peri/postmenopausal depression.