产后抑郁（PPD）严重影响产妇身心健康，但病因机制未明，无有效防治手段。PPD的发生与环境及基因易感性有关，GABAA受体功能异常是其主要病理特征，但调控机理不详。表观遗传学为阐明基因和环境相互作用提供了手段，长链非编码RNA（lncRNA）因有特殊二级结构，可从表观遗传多层次快速调控基因，但其影响GABAA受体基因表达及与PPD发生之间的关系不明。课题组前期发现PPD导致内侧前额叶（mPFC）GABAA受体δ和γ2亚基表达低下，并确证PPD模型组mPFC中537个lncRNA差异群和可能参与δ和γ2亚基表达调控的2个lncRNA。我们拟结合基础和临床研究，探索：1）关键lncRNA调控δ和γ2亚基的表观遗传分子机制；2）关键lncRNA对PPD抑郁行为的影响及机理；3）寻找PPD患者血样特征性lncRNA。旨在阐明PPD中lncRNA调控GABAA受体可塑性的机理和发现PPD潜在标志物。

Postpartum depression (PPD) seriously threatens the physical and mental health of parturient, however, the etiology remains unclear, and there is no effective prevention and treatment measures for PPD at present. Previous reports suggested that the dysfunction of GABAA receptor pathologically characters the development of PPD, but the underlying mechanism is still unclear. Both genetic and environmental factors are involved in the development of PPD, and the proposal of epigenetics helps to elucidate the interaction between gene and environment. Owing to the special secondary structure, long non-coding RNA (lncRNA) rapidly regulates the expression of its target gene expression at epigenetic, transcriptional and post-transcriptional levels. However, the precise regulation mechanism of lncRNA on GABAA receptor and its contribution to the pathogenesis of PPD remain to be clarified. We have already found that the expression of δ and γ2 subunits of GABAA receptor in mPFC decreased, and revealed that there were 537 differential expressions of lncRNA, among which, 2 lncRNA might be involved in the regulation of δ and γ2 subunit in mPFC of PPD rats. Based upon the previous findings, we plan to clarify the following three questions from basic research to clinical practice: 1) to find the key lncRNA and its underlying epigenetic molecular mechanism on the regulation of δ and γ2 subunits; 2) to clarify the effect and underlying mechanism of key lncRNA on the development of depressive-like behaviors of PPD rats; and 3) to find the characteristic lncRNA in blood samples of PPD patients. The present study is aimed to elucidate the mechanism of lncRNA on the regulation of GABAA receptor in PPD and discover potential biomarkers of PPD.