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Resveratrol ameliorates estrogen deficiency-induced depression- and anxiety-like behaviors and hippocampal inflammation in mice

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Abstract

Rationale

Resveratrol (RSV) has been indicated to exhibit beneficial effects on depression and anxiety treatment by suppression of inflammatory processes. Depression triggered by deficiency of estrogen and anxiety-like behaviors are associated with inflammation. The role of RSV in ovariectomized mice is unclear.

Objectives

We examine whether the RSV, a Sirt1 activator, alleviates ovariectomy-induced anxiety- and depression-like behaviors through the inhibition of inflammatory processes.

Methods

Female C57BL/6J mice (6–8 weeks of age, 17–20 g) were ovariectomized and treated with RSV at a dose of 20 mg/kg for 2 weeks. Depression- and anxiety-like behaviors were compared with vehicle-injected control animals. Immunohistochemistry and qPCR were used to detect inflammation in the hippocampal region.

Results

Ovariectomized mice were observed to suffer from anxiety- and depression-like behaviors. These effects were attenuated by treatment with RSV. Immunohistochemical staining results showed that RSV could reverse the increase of microglial activation in the hippocampal dentate gyrus. At a molecular level, RSV inhibited the activation of NLRP3 and NF-κB in the hippocampal region caused by deficiency of estrogen.

Conclusions

RSV suppressed the production of inflammatory cytokines by enhancing Sirt1 levels. Our findings indicated that RSV-induced Sirt1 activation counteracted estrogen deficiency-induced psychobehavioral changes via inhibition of inflammatory processes in the hippocampus. In anxiety and depression disorders, RSV is supposed to be an effective treatment for postmenopausal changes.

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Funding

The study was funded by the National Key R&D Program of China (2017YFE0103700) and the National Nature Science Foundation of China (No. 81371197).

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Authors and Affiliations

  1. Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, 400038, China

    Tianyao Liu, Yuanyuan Ma, Ruiyu Zhang, Hongyu Zhong, Lian Wang, Jinghui Zhao, Ling Yang & Xiaotang Fan

  2. Department of Histology and Embryology, Third Military Medical University, Chongqing, China

    Tianyao Liu & Ruiyu Zhang

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  1. Tianyao Liu
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  2. Yuanyuan Ma
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  3. Ruiyu Zhang
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  4. Hongyu Zhong
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  5. Lian Wang
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  6. Jinghui Zhao
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  7. Ling Yang
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  8. Xiaotang Fan
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Correspondence to Xiaotang Fan.

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Liu, T., Ma, Y., Zhang, R. et al. Resveratrol ameliorates estrogen deficiency-induced depression- and anxiety-like behaviors and hippocampal inflammation in mice. Psychopharmacology 236, 1385–1399 (2019). https://doi.org/10.1007/s00213-018-5148-5

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  • DOI: https://doi.org/10.1007/s00213-018-5148-5

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