No abstract

Postpartum depressive symptom (PDS) is a common psychological and mental disorder after giving birth. Our previous studies showing the application of dexmedetomidine, an α2-AR agonist, can significantly improve maternal sleep, as well as relieve and reduce the incidence of PDS. This study investigated the association between α2AAR gene polymorphisms and PDS. A total of 568 cesarean section patients were enrolled; the incidence of PDS is 18.13% (103 with PDS, 465 with non-PDS). The Edinburgh Postpartum Depression Scale score ≥10 was used to diagnose PDS at 42 days after delivery. The single-nucleotide polymorphisms of α2AR were sequenced by pyrosequencing. The effect of rs13306146 A > G polymorphism on α2AR transcription and the regulation of miR-646 on α2AR expression were assessed by dual luciferase reporter assays or gene transfection. Increased stress during pregnancy, poor relationship between mother-in-law and daughter-in-law, spousal relationship, domestic violence, antenatal depression, self-harm ideation, and stressful life events were all associated with increased PDS incidence (p < 0.05). The logistic regression analysis found that the α2AAR rs13306146 polymorphism was associated with PDS after adjusting confounding variables. The transcriptional function of the α2AAR rs13306146 A allele was decreased compared with the G allele, and the α2AAR expression level was correspondingly decreased (p < 0.05), as the strongest binding ability of miR-646 to the α2AAR rs13306146 AA genotype. The effect of α2AAR rs13306146 A > G polymorphism may change the binding ability of miR-646 at the 3′UTR of the α2AAR gene, affecting the expression of α2AAR. This study supports the involvement of the norepinephrine system in the pathogenesis of PDS. Genotypes of α2AAR may be novel and useful biomarkers for PDS.

Postoperative cognitive dysfunction (POCD) after cardiopulmonary bypass is a serious complication that can lead to personality changes, memory loss, reduction in the ability to learn, and other central nervous system dysfunctions. In recent years, there have been improvements in measures to protect the brain during surgery, although the incidence of cognitive dysfunction after cardiac surgery remains high (33 to 83% short-term and 20 to 60% long-term cognitive dysfunction). Despite the large amount of basic and clinical research on the incidence of POCD, its exact pathogenesis and complexity are not clear. Many studies have shown that the kynurenine pathway (KP) and cognitive function in humans are closely related. Some reports also show that the imbalance of some metabolites of the KP such as kynurenic acid and quinolinic acid (QUIN), which act in dynamic equilibrium under physiologic conditions, have effects on the central nervous system and can significantly affect cognitive function. Further studies have shown that inflammatory mediators may act on key enzymes of the KP causing KP-induced disorders. Severe inflammatory reaction occurs in patients undergoing cardiopulmonary bypass, which triggers metabolic pathways that are closely related to changes in cognitive function. In this review, we summarize that inflammation-induced metabolic kynurenine (KYN) pathway disorders are likely to have an important role in incidence of POCD after CPB surgery.