1. Academic Validation
  2. Resveratrol alleviates postpartum depression-like behavior by activating autophagy via SIRT1 and inhibiting AKT/mTOR pathway

Resveratrol alleviates postpartum depression-like behavior by activating autophagy via SIRT1 and inhibiting AKT/mTOR pathway

  • Behav Brain Res. 2022 Nov 7;438:114208. doi: 10.1016/j.bbr.2022.114208.
Shan Ye 1 Li Fang 2 Shiyi Xie 3 Yan Hu 1 Shijia Chen 4 Nashwa Amin 4 Marong Fang 4 Zhiying Hu 5
Affiliations

Affiliations

  • 1 The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
  • 2 Department of Obstetrics and Gynecology, Integrated Chinese and West Medicine Hospital Affiliated to Zhejiang Chinese Medicine University, Hangzhou, Zhejiang, China.
  • 3 Department of Obstetrics and Gynecology, First people's Hospital of Linping District, Hangzhou, Zhejiang, China.
  • 4 Institute of Neuroscience, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
  • 5 Department of Obstetrics and Gynecology, Integrated Chinese and West Medicine Hospital Affiliated to Zhejiang Chinese Medicine University, Hangzhou, Zhejiang, China. Electronic address: huzhiying@zcmu.edu.cn.
Abstract

Background: Postpartum depression (PPD) causes maternal mortality, and has a high disability rate. In recent years, studies have suggested the SIRT1 gene to be involved in the pathogenesis of depression. Resveratrol (RSV), an activator of SIRT1, has been investigated in depressive behavior. However, its effect on PPD remains to be thoroughly elucidated.

Methods: We employed a mice model with bilateral oophorectomy combined with hormone-simulated pregnancy to assess postpartum depression-like behavior. The behavioral tests were performed 2 days after the withdrawal of estradiol benzoate. RSV was administered subcutaneously to the PPD model mice. Several behavioral tests were executed, including the open field test, forced swimming test, and tail suspension test. Western blot analyses and immunofluorescence staining were used to evaluate protein expression levels of SIRT1, Autophagy markers, and the Akt/mTOR.

Results: Postpartum depressive-like behavior was triggered following the withdrawal of estradiol benzoate after hormone-stimulated-pregnancy. RSV improved postpartum depressive-like behavior of mice via its upregulation of the SIRT1 and Autophagy markers, such as Beclin1, ATG5 and LC3B. Also, the downregulation of the p62 protein expression was observed. More importantly, we also detected the inhibition of phosphorylated Akt and mTOR in the hippocampus of postpartum depressive-like mice.

Conclusion: RSV could alleviate postpartum depression-like behavior in mice by stimulating the SIRT1, induce Autophagy and inhibit the Akt/ mTOR signaling pathway.

Keywords

Autophagy; Postpartum depression; Resveratrol; SIRT1; mTOR.

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