Xu Fang, Wu Hui, Xie Linghua, Chen Qing, Xu Qi, Sun Lihong, Li Hua, Xie Jiaqian, Chen Xinzhong
Department of Anesthesia, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Mol Neurosci. 2023 Jan 26;15:1109458. doi: 10.3389/fnmol.2022.1109458. eCollection 2022.
Postpartum depression (PPD) is a common neuropsychiatric disorder characterized by depression and comorbid anxiety during the postpartum period. PPD is difficult to treat because of its elusive mechanisms. Epigallocatechin-3-gallate (EGCG), a component of tea polyphenols, is reported to exert neuroprotective effects in emotional disorders by reducing inflammation and apoptosis. However, the effect of EGCG on PPD and the underlying mechanism are unknown.
We used a mouse model of PPD established by exposing pregnant mice to gestational stress. Open field, forced swimming and tail suspension tests were performed to investigate the anxiety and depression-like behaviors. Immunohistochemical staining was used to measure the c-fos positive cells. The transcriptional levels of hippocampal semaphorin3A(sema3A), (glycogen synthase kinase 3-beta)GSK3β and collapsin response mediator protein 2(CRMP2) were assessed by RT-PCR. Alterations in protein expression of Sema3A, GSK3β, p-GSK3β, CRMP2 and p-CRMP2 were quantified by western blotting. EGCG was administrated to analyze its effect on PPD mice.
Gestational stress induced anxiety and depression-like behaviors during the postpartum period, increasing Sema3A expression while decreasing that of phosphorylated GSK3β as well as c-Fos in the hippocampus. These effects were reversed by systemic administration of EGCG.
Thus, EGCG may alleviate anxiety and depression-like behaviors in mice by downregulating Sema3A and increasing GSK3β phosphorylation in the hippocampus, and has potential application in the treatment of PPD.
产后抑郁症（PPD）是一种常见的神经精神障碍，其特征为产后出现抑郁及合并焦虑症状。由于其发病机制难以捉摸，PPD难以治疗。表没食子儿茶素没食子酸酯（EGCG）是茶多酚的一种成分，据报道其可通过减轻炎症和细胞凋亡对情绪障碍发挥神经保护作用。然而，EGCG对PPD的影响及其潜在机制尚不清楚。
我们使用通过使怀孕小鼠遭受孕期应激建立的PPD小鼠模型。进行旷场试验、强迫游泳试验和悬尾试验以研究焦虑和抑郁样行为。采用免疫组织化学染色法检测c-fos阳性细胞。通过RT-PCR评估海马中信号素3A（sema3A）、糖原合酶激酶3β（GSK3β）和塌陷反应介导蛋白2（CRMP2）的转录水平。通过蛋白质免疫印迹法定量分析Sema3A、GSK3β、磷酸化GSK3β、CRMP2和磷酸化CRMP2的蛋白表达变化。给予EGCG以分析其对PPD小鼠的影响。
孕期应激导致产后出现焦虑和抑郁样行为，增加海马中Sema3A的表达，同时降低磷酸化GSK3β以及c-Fos的表达。全身给予EGCG可逆转这些作用。
因此，EGCG可能通过下调Sema3A并增加海马中GSK3β的磷酸化来减轻小鼠的焦虑和抑郁样行为，在PPD的治疗中具有潜在应用价值。
