Association of miR-335-5p Dysregulation with Postpartum Depression: Clinical Findings and Experimental Validation in a Mouse Model

Introduction: Postpartum depression (PPD) is a common and debilitating mood disorder that affects many mothers worldwide, presenting significant challenges to maternal and infant health. This study investigated the clinical relevance and functional mechanisms of miR-335-5p in PPD, to identify novel therapeutic strategies. Methods: miR-335-5p expression was measured by RT-qPCR. Diagnostic value and clinical correlations of miR-335-5p were evaluated using ROC curve analysis, Spearman correlation, and logistic regression. A PPD mouse model was established to investigate the effects of miR-335-5p on depressive-like behaviors. Oxidative stress markers and inflammatory factors were assessed using commercial detection kits and ELISA, respectively. Potential target genes of miR-335-5p were predicted via online databases and further subjected to GO and KEGG enrichment analyses. Results: Serum miR-335-5p was upregulated in patients with PPD and showed high diagnostic accuracy (AUC=0.862). Its expression correlated with sleep disorders, and both were identified as PPD risk factors. Similarly, miR-335-5p was elevated in a PPD mouse model. Knockdown of miR-335-5p alleviated depressive-like behaviors, including reduced rearing episodes, decreased total distance, increased feeding latency, and prolonged immobility time. Furthermore, miR-335-5p inhibition increased catalase activity, glutathione levels, and total antioxidant capacity, while reducing TNF-α, IL-6, and IL-1β levels. The targets of miR-335-5p were enriched in the circadian rhythm and MAPK signaling pathways. Conclusions: Elevated miR-335-5p expression represents a potential biomarker for PPD and is associated with sleep disorders. In mouse models, miR-335-5p knockdown alleviates depressive-like behaviors, decreases oxidative stress, and inhibits inflammatory responses, thereby offering mechanistic insights into PPD.