Long noncoding RNA NONHSAG045500 regulates serotonin transporter to ameliorate depressive-like behavior via the cAMP–PKA–CREB signaling pathway in a model of perinatal depression

Abstract

Objective Perinatal depression (PND) is the most common complication of childbirth and negatively affects the mother. Long noncoding RNA (lncRNA) NONHSAG045500 inhibits the expression of 5-hydroxytryptamine (5-HT) transporter (i.e. serotonin transporter [SERT]) and produces an antidepressant effect. This study aimed to identify a link between the lncRNA NONHSAG045500 and the pathogenesis of PND. Methods Female C57BL/6 J mice were divided into normal control group (control group, n = 15), chronic unpredictable stress (CUS) model group (PND group, n = 15), lncRNA NONHSAG045500-overexpressed group (LNC group, sublingual intravenous injection of NONHSAG045500 overexpression cells for 7 days, n = 15), and escitalopram treatment group (i.e. the selective serotonin reuptake inhibitor [SSRI] group, with escitalopram administered from the 10th day after pregnancy to the 10th day after delivery, n = 15). Control group mice were conceived normally, whereas, in the other groups, a CUS model was established before mice were conceived. Depressive-like behaviour was assessed via sucrose preference, forced swimming, and open-field tests. The expression levels of 5-HT, SERT, and cAMP–PKA–CREB pathway-related proteins in the prefrontal cortex were detected on the 10th day after delivery. Results Mice in the PND group exhibited significant depressive-like behaviours compared with those in the control group, indicating that the PND model was successfully established. The expression of lncRNA NONHSAG045500 was markedly decreased in the PND group compared with that in the control group. After treatment, both LNC and SSRI groups showed a significant improvement in depression-like behaviour, and the expression of 5-HT in the prefrontal cortex was increased in these groups compared with that in the PND group. In addition, the LNC group displayed lower expression of SERT and higher expression of cAMP, PKA, and CREB when in comparison to PND group. Conclusion NONHSAG045500 mediates the development of PND mainly by activating the cAMP–PKA–CREB pathway, increasing the level of 5-HT, and decreasing the expression of SERT.