Restoring Wnt signaling in a hormone-simulated postpartum depression model remediated imbalanced neurotransmission and depressive-like behaviors

Binglu Ye; Yawei Yuan; Rui Liu; Haitao Zhou; Yujie Li; Zhihao Sheng; Tianyu Li; Bing Zhang; Zhendong Xu; Yang Li; Zhiqiang Liu

doi:10.1186/s10020-023-00697-4

Restoring Wnt signaling in a hormone-simulated postpartum depression model remediated imbalanced neurotransmission and depressive-like behaviors

Mol Med. 2023 Jul 25;29(1):101. doi: 10.1186/s10020-023-00697-4.

Authors

Binglu Ye^#¹, Yawei Yuan^#¹, Rui Liu^#¹, Haitao Zhou^{2

3}, Yujie Li¹, Zhihao Sheng¹, Tianyu Li^{1

2}, Bing Zhang^{1

4}, Zhendong Xu^{5

6}, Yang Li^{7

8

9}, Zhiqiang Liu^{10

11}

Affiliations

¹ Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China.
² State Key Laboratory of Drug Research and Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
³ University of Chinese Academy of Sciences, No.9A Yuquan Road, Beijing, 100049, China.
⁴ Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China.
⁵ Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China. btxzd123@126.com.
⁶ Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China. btxzd123@126.com.
⁷ State Key Laboratory of Drug Research and Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. liyang@simm.ac.cn.
⁸ University of Chinese Academy of Sciences, No.9A Yuquan Road, Beijing, 100049, China. liyang@simm.ac.cn.
⁹ National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China. liyang@simm.ac.cn.
¹⁰ Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China. drliuzhiqiang@163.com.
¹¹ Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China. drliuzhiqiang@163.com.

^# Contributed equally.

Abstract

Background: Postpartum depression (PPD) is a prevalent mental disorder that negatively impacts mothers and infants. The mechanisms of vulnerability to affective illness in the postpartum period remain largely unknown. Drastic fluctuations in reproductive hormones during the perinatal period generally account for triggering PPD. However, the molecular mechanism underlying the PPD-like behaviors induced by the fluctuations in hormones has rarely been reported.

Methods: We utilized hormones-simulated pseudopregnancy (HSP) and hormones-simulated postpartum period (HSPP) rat models to determine how drastic fluctuations in hormone levels affect adult neurotransmission and contribute to depressive-like behaviors. The electrophysiological response of CA1 pyramidal neurons was evaluated by whole-cell patch clamping to identify the hormone-induced modulations of neurotransmission. The statistical significance of differences was assessed with One-way ANOVA and t-test (p < 0.05 was considered significant).

Results: Reproductive hormones withdrawal induced depressive-like behaviors and disturbed the balance of excitatory and inhibitory transmission in the pyramidal neurons in the hippocampus. Molecular analyses revealed that the blunted Wnt signaling might be responsible for the deficits of synaptic transmission and behaviors. Activation of Wnt signaling increased excitatory and inhibitory synaptic transmission in the hippocampus. Reactivation of Wnt signaling alleviated the anhedonic behaviors and abnormal synaptic transmission.

Conclusions: Restoring Wnt signaling in the hormones-simulated postpartum period rat models remediated depression-related anhedonia symptoms and rebalanced the excitation/inhibition ratio by collectively enhancing the plasticity of GABAergic and glutamatergic synapses. The investigations carried out in this research might provide an alternative and prospective treatment strategy for PPD.

Keywords: CA1; Hippocampus; Neurotransmission; Postpartum depression (PPD); Wnt signaling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Depression, Postpartum*
Female
Hippocampus
Hormones
Humans
Pregnancy
Rats
Synaptic Transmission
Wnt Signaling Pathway

Substances

Hormones