MicroRNA-99a is a Potential Target for Regulating Hypothalamic Synaptic Plasticity in the Peri/Postmenopausal Depression Model
MicroRNA-99a is a Potential Target for Regulating Hypothalamic Synaptic Plasticity in the Peri/Postmenopausal Depression Model
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MicroRNA-99a 是调节围绝经期/绝经后抑郁模型下丘脑突触可塑性的潜在靶点
DOI：
10.3390/cells8091081
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发表时间：
2019-09
期刊：
影响因子：
6
通讯作者：
Sun Xiu-Lan
中科院分区：
文献类型：
--
作者：
Yang Jin;Zhang Ling;Cao Lu-Lu;Qi Jun;Li Ping;Wang Xi-Peng;Sun Xiu-Lan
越来越多的证据表明，更年期妇女患抑郁症的趋势越来越明显。然而，绝经期抑郁症的发病机制仍不清楚。因此，本文的目的是揭示绝经后抑郁症的病理机制，通过使用一种新的绝经后抑郁症模型的两步卵巢切除术加慢性轻度应激（CMS）。代谢室和血清激素/细胞因子测定结果显示，绝经后抑郁小鼠表现出内分泌和代谢紊乱。电生理记录表明，海马突触传递受损。与假手术组相比，绝经后抑郁模型小鼠下丘脑microRNA-99 a（miR-99 a）水平显著降低，其靶蛋白FK 506结合蛋白51（FKBP 51）显著增加;而下丘脑室旁核（PVN）孕酮受体（PR）核转位减少。此外，突触蛋白，包括突触后密度蛋白95（PSD-95）和突触素（SYN），在下丘脑中显示出类似的减少。因此，本工作表明，miR-99 a可能参与下丘脑突触可塑性的调节，并且它可能是绝经后抑郁症的潜在治疗靶点。
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.
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影响因子：
5.4
作者：
Hoyt, Lindsay Till;Falconi, April M.
通讯作者：
Falconi, April M.
DOI：
10.6118/jmm.2017.23.3.160
发表时间：
2017-12
期刊：
Journal of menopausal medicine
影响因子：
--
作者：
Fattah A
通讯作者：
Fattah A
DOI：
10.1073/pnas.1015691107
发表时间：
2010-11-23
影响因子：
11.1
作者：
Magill, Stephen T.;Cambronne, Xiaolu A.;Goodman, Richard H.
通讯作者：
Goodman, Richard H.
DOI：
10.1172/jci123689
发表时间：
2019-05
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Kun Zhang;Qi Yang;Le Yang;Yan-jiao Li;Xin-shang Wang;Yu-jiao Li;Rui Dang;Shao-yu Guan;Yan-Yan Guo-Yan;Ting Sun;Yu-Mei Wu;An Liu;Yan Zhang;Shui-bing Liu;Ming-gao Zhao
通讯作者：
Kun Zhang;Qi Yang;Le Yang;Yan-jiao Li;Xin-shang Wang;Yu-jiao Li;Rui Dang;Shao-yu Guan;Yan-Yan Guo-Yan;Ting Sun;Yu-Mei Wu;An Liu;Yan Zhang;Shui-bing Liu;Ming-gao Zhao
影响因子：
5.6
作者：
Tomasetti C;Iasevoli F;Buonaguro EF;De Berardis D;Fornaro M;Fiengo AL;Martinotti G;Orsolini L;Valchera A;Di Giannantonio M;de Bartolomeis A
通讯作者：
de Bartolomeis A