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The Antidepressant Effects of Resveratrol are Accompanied by the Attenuation of Dendrite/Dendritic Spine Loss and the Upregulation of BDNF/p-cofilin1 Levels in Chronic Restraint Mice

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Abstract

Depression afflicts more than 300 million people worldwide, but there is currently no universally effective drug in clinical practice. In this study, chronic restraint stress (CRS)-induced mice depression model was used to study the antidepressant effects of resveratrol and its mechanism. Our results showed that resveratrol significantly attenuated depression-like behavior in mice. Consistent with behavioral changes, resveratrol significantly attenuated CRS-induced reduction in the density of dendrites and dendritic spines in both hippocampus and medial prefrontal cortex (mPFC). Meanwhile, in hippocampus and mPFC, resveratrol consistently alleviated CRS-induced cofilin1 activation by increasing its ser3 phosphorylation. In addition, cofilin1 immunofluorescence distribution in neuronal inner peri-membrane in controls, and cofilin1 diffusely distribution in the cytoplasm in CRS group were common in hippocampus. However, the distribution of cofilin1 in mPFC was reversed. Pearson’s correlation analysis revealed that there was a significant positive correlation found between the sucrose consumption in sucrose preference test and the dendrite density in multiple sub-regions of hippocampus and mPFC, and a significant negative correlation between the immobility time in tail suspension test and the dendrite/dendritic spine density in several different areas of hippocampus and mPFC. P-cofilin1 was significantly positively correlated with the overall dendritic spine density in mPFC as well as with the overall dendrite density or BDNF in the hippocampus. Our results suggest that the BDNF/cofilin1 pathway, in which cofilin1 may be activated in a brain-specific manner, was involved in resveratrol’s attenuating the dendrite and dendritic spine loss and behavioral abnormality.

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Acknowledgments

We thank Pref Jiang-Ning Zhou for providing us with transgenic mice (B6.Cg-TgN (Thy-YFP-H) 2Jrs), Mr. Ke-Qing Zhou for help in the experimental methods, Ms. Yan-Qing Qiu and Ying Tian for help in the experiment, and Mr. Hao Yan and Ms. Xiao-Yan Ma for help in the confocal photomicrographs. This work was supported by the National Natural Science Foundation of China (No. 30470537), the Natural Science Foundation of the Department of Education, Anhui Province (ZD2008006-1), Anhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Diseases, Anhui Provincial Key Laboratory of the Conservation and Exploitation of Biological Resources, Key Laboratory of Biomedicine in Gene Diseases and Health of Anhui Higher Education Institutes and the Innovation Team of Scientific Research Platform in Anhui Universities.

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  1. College of Life Science, Anhui Normal University, No. 1 Beijing East Road, Wuhu, 241000, China

    Jing-Jing Chen, Jun-Xian Shen, Zong-Hao Yu, Chuan Pan, Fei Han, Xiu-Ling Zhu, Hui Xu, Rui-Ting Xu, Tong-Yao Wei & Ya-Ping Lu

  2. Department of Anatomy, Wannan Medical College, No. 22 Wenchang West Road, Wuhu, 241002, China

    Xiu-Ling Zhu

  3. Anhui College of Traditional Chinese Medicine, No. 18 Wuxiashan West Road, Wuhu, 241002, China

    Hui Xu

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Chen, JJ., Shen, JX., Yu, ZH. et al. The Antidepressant Effects of Resveratrol are Accompanied by the Attenuation of Dendrite/Dendritic Spine Loss and the Upregulation of BDNF/p-cofilin1 Levels in Chronic Restraint Mice. Neurochem Res 46, 660–674 (2021). https://doi.org/10.1007/s11064-020-03200-1

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