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Restoring Wnt signaling in a hormone-simulated postpartum depression model remediated imbalanced neurotransmission and depressive-like behaviors
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 generall...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10369844/ https://www.ncbi.nlm.nih.gov/pubmed/37491227 http://dx.doi.org/10.1186/s10020-023-00697-4 |
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author | Ye, Binglu Yuan, Yawei Liu, Rui Zhou, Haitao Li, Yujie Sheng, Zhihao Li, Tianyu Zhang, Bing Xu, Zhendong Li, Yang Liu, Zhiqiang |
author_facet | Ye, Binglu Yuan, Yawei Liu, Rui Zhou, Haitao Li, Yujie Sheng, Zhihao Li, Tianyu Zhang, Bing Xu, Zhendong Li, Yang Liu, Zhiqiang |
author_sort | Ye, Binglu |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-023-00697-4. |
format | Online Article Text |
id | pubmed-10369844 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-103698442023-07-27 Restoring Wnt signaling in a hormone-simulated postpartum depression model remediated imbalanced neurotransmission and depressive-like behaviors Ye, Binglu Yuan, Yawei Liu, Rui Zhou, Haitao Li, Yujie Sheng, Zhihao Li, Tianyu Zhang, Bing Xu, Zhendong Li, Yang Liu, Zhiqiang Mol Med Research Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-023-00697-4. BioMed Central 2023-07-25 /pmc/articles/PMC10369844/ /pubmed/37491227 http://dx.doi.org/10.1186/s10020-023-00697-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Ye, Binglu Yuan, Yawei Liu, Rui Zhou, Haitao Li, Yujie Sheng, Zhihao Li, Tianyu Zhang, Bing Xu, Zhendong Li, Yang Liu, Zhiqiang Restoring Wnt signaling in a hormone-simulated postpartum depression model remediated imbalanced neurotransmission and depressive-like behaviors |
title | Restoring Wnt signaling in a hormone-simulated postpartum depression model remediated imbalanced neurotransmission and depressive-like behaviors |
title_full | Restoring Wnt signaling in a hormone-simulated postpartum depression model remediated imbalanced neurotransmission and depressive-like behaviors |
title_fullStr | Restoring Wnt signaling in a hormone-simulated postpartum depression model remediated imbalanced neurotransmission and depressive-like behaviors |
title_full_unstemmed | Restoring Wnt signaling in a hormone-simulated postpartum depression model remediated imbalanced neurotransmission and depressive-like behaviors |
title_short | Restoring Wnt signaling in a hormone-simulated postpartum depression model remediated imbalanced neurotransmission and depressive-like behaviors |
title_sort | restoring wnt signaling in a hormone-simulated postpartum depression model remediated imbalanced neurotransmission and depressive-like behaviors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10369844/ https://www.ncbi.nlm.nih.gov/pubmed/37491227 http://dx.doi.org/10.1186/s10020-023-00697-4 |
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