Comparison of the estrogen withdrawal and chronic restraint stress and the maternal separation in mice postpartum depression modeling

Background

Postpartum depression (PPD) is a severe psychological and psychiatric disorder that affects women during the perinatal period. Animal models play a crucial role in studying the pathogenesis of PPD. However, a comprehensive comparison of the distinctive features of estrogen withdrawal (EW), chronic restraint stress (CRS), and maternal separation (MS) rodent models, which are commonly used in PPD research, is lacking.

Methods

Three models of PPD were developed in this study, and the success of modeling was judged by the sucrose preference test (SPT) and the tail suspension test (TST). SPT, open field test (OFT), elevated plus maze (EPM), forced swim test (FST), and TST were performed sequentially at the end of the molding process. Reproductive hormone changes in the peripheral blood, changes in GPR30 expression and GPR30⁺ astrocytes in the hippocampus were also assessed.

Results

Data from the EW and CRS experiments showed a significant reduction in SPT and prolonging in the immobility time of the TST in subjects after modeling compared to baseline values. In all three models, levels of estradiol showed a significant decrease, whereas levels of progesterone statistically decreased and prolactin significantly increased only in the CRS and MS mice. Western-blot results showed a significant decrease in GPR30 expression in hippocampal regions of EW and CRS mice, while MS mice did not show differences. The EW and CRS models expressed less GPR30⁺ astrocytes and the morphological complexity of astrocytes was significantly reduced in the hippocampal CA1 region.

Conclusion

The CRS model showed more obvious parameter changes and was closer to clinical PPD, which may be more appropriate to study PPD.