Abstract
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.
Highlights
Depression is a chronical emotional disorder characterized by complicated pathophysiological and neuroendocrine alterations
We found that the peri/postmenopausal depression mouse model showed a sharper decline in levels of synaptic proteins (PSD-95) and synaptophysin in the paraventricular nucleus (PVN) of the hypothalamus compared to the chronic mild stress (CMS) model (Figure 5A–D)
Our study focused on the occurrence of depression during menopausal transition rather than focusing on the premenopause or postmenopause period
Summary
Depression is a chronical emotional disorder characterized by complicated pathophysiological and neuroendocrine alterations. Beginning during adolescence and throughout women’s lives, women are twice as likely to suffer from depression than men, and they are especially at high risk during their menopause transition [2]. During this period, women undergo rapid hormonal changes, which may affect the activity of neurons in the brain, leading to mood swings and even depression [3,4]. Menopausal depression is still poorly understood and is a controversial topic [5,6] Hormone treatment, such as estrogen replacement therapy [7], only
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