I'm sure your doctor would never approve of using red wine to get resveratrol. So don't even bother asking and enjoy red wine with friends. I do, so far in Italy, France, Spain and Portugal, soon Australia.
The Antidepressant Effect of Resveratrol Is Related to Neuroplasticity Mediated by the ELAVL4-Bdnf mRNA Pathway
1
Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China
2
Department of Psychiatry, Institute of Neuropsychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China
3
Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430071, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work as co-first authors.
Int. J. Mol. Sci. 2025, 26(3), 1113; https://doi.org/10.3390/ijms26031113
Submission received: 11 December 2024
/
Revised: 17 January 2025
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Accepted: 21 January 2025
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Published: 27 January 2025
(This article belongs to the Special Issue Bioactive Compounds in Human Brain Structures and Diseases: 2nd Edition)
Abstract
Resveratrol, a plant-derived polyphenol,
exhibits significant antidepressant effects and notably enhances
neuroplasticity in neurological diseases. However, whether the
antidepressant function of resveratrol is related to neuroplasticity
remains uncertain, and the underlying mechanisms is poorly understood.
This study aims to investigate the role and mechanism of resveratrol in
neuroplasticity in depression. Here, we adopted the chronic
unpredictable mild stress (CUMS) model and resveratrol intervention by
oral gavage. Thereafter, behavioral tests confirmed resveratrol’s
antidepressant effect, and Nissl staining, Golgi staining, and Western
blotting (WB) were employed to assess the neuronal plasticity. Moreover,
proteomic analysis and WB were used to screen and identify the key
proteins. To investigate the downstream target of ELAV-like RNA-binding
protein 4 (ELAVL4) (one of candidate genes), the RNA Interactome
Database and the National Center for Biotechnology Information databases
were utilized to predict the targets of ELAVL4. Finally, Quantitative
PCR, WB, and Immunofluorescence were used to verify the prediction. Our
results indicate that resveratrol alleviates CUMS-induced
depressive-like behaviors accompanied by the restoration of impaired
hippocampal neuroplasticity. Then, proteomic analysis shows that 351
differentially expressed proteins (DEPs) decrease after CUMS, while 24
DEPs increase remarkably with the resveratrol treatment. Among which,
ELAVL4 is downregulated by CUMS, simultaneously increasing after
resveratrol intervention, which acts as a protective protein in this
process. Finally, brain-derived neurotrophic factor (Bdnf)
mRNA is predicted to be the potential target of ELAVL4 and validated by
molecular technologies. In conclusion, our findings demonstrate that
resveratrol’s antidepressant efficacy is closely associated with ELAVL4,
an RNA-binding protein, a mediated neuroplasticity pathway, potentially
intersecting with the Bdnf mRNA. Overall, this research sheds light on the role of the ELAVL4-Bdnf
mRNA pathway through neuroplasticity in resveratrol’s antidepressant
action, which provides an mRNA regulation perspective for the
development of novel antidepressants and understanding depression
pathology.
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