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Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents

The transcription factor erythroid 2-related factor 2 (Nrf2) and brain-derived neurotrophic factor (BDNF) play a key role in depression. However, the molecular mechanisms underlying the crosstalk between Nrf2 and BDNF in depression remain unclear. We examined whether Nrf2 regulates the transcription...

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Autores principales: Yao, Wei, Lin, Song, Su, Jin, Cao, Qianqian, Chen, Yueyue, Chen, Jiaxu, Zhang, Zhentao, Hashimoto, Kenji, Qi, Qi, Zhang, Ji-chun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904924/
https://www.ncbi.nlm.nih.gov/pubmed/33627628
http://dx.doi.org/10.1038/s41398-021-01261-6
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author Yao, Wei
Lin, Song
Su, Jin
Cao, Qianqian
Chen, Yueyue
Chen, Jiaxu
Zhang, Zhentao
Hashimoto, Kenji
Qi, Qi
Zhang, Ji-chun
author_facet Yao, Wei
Lin, Song
Su, Jin
Cao, Qianqian
Chen, Yueyue
Chen, Jiaxu
Zhang, Zhentao
Hashimoto, Kenji
Qi, Qi
Zhang, Ji-chun
author_sort Yao, Wei
collection PubMed
description The transcription factor erythroid 2-related factor 2 (Nrf2) and brain-derived neurotrophic factor (BDNF) play a key role in depression. However, the molecular mechanisms underlying the crosstalk between Nrf2 and BDNF in depression remain unclear. We examined whether Nrf2 regulates the transcription of Bdnf by binding to its exon I promoter. Furthermore, the role of Nrf2 and BDNF in the brain regions from mice with depression-like phenotypes was examined. Nrf2 regulated the transcription of Bdnf by binding to its exon I promoter. Activation of Nrf2 by sulforaphane (SFN) showed fast-acting antidepressant-like effects in mice by activating BDNF as well as by inhibiting the expression of its transcriptional repressors (HDAC2, mSin3A, and MeCP2) and revising abnormal synaptic transmission. In contrast, SFN did not affect the protein expression of BDNF and its transcriptional repressor proteins in the medial prefrontal cortex (mPFC) and hippocampus, nor did it reduce depression-like behaviors and abnormal synaptic transmission in Nrf2 knockout mice. In the mouse model of chronic social defeat stress (CSDS), protein levels of Nrf2 and BDNF in the mPFC and hippocampus were lower than those of control and CSDS-resilient mice. In contrast, the protein levels of BDNF transcriptional repressors in the CSDS-susceptible mice were higher than those of control and CSDS-resilient mice. These data suggest that Nrf2 activation increases the expression of Bdnf and decreases the expression of its transcriptional repressors, which result in fast-acting antidepressant-like actions. Furthermore, abnormalities in crosstalk between Nrf2 and BDNF may contribute to the resilience versus susceptibility of mice against CSDS.
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spelling pubmed-79049242021-03-11 Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents Yao, Wei Lin, Song Su, Jin Cao, Qianqian Chen, Yueyue Chen, Jiaxu Zhang, Zhentao Hashimoto, Kenji Qi, Qi Zhang, Ji-chun Transl Psychiatry Article The transcription factor erythroid 2-related factor 2 (Nrf2) and brain-derived neurotrophic factor (BDNF) play a key role in depression. However, the molecular mechanisms underlying the crosstalk between Nrf2 and BDNF in depression remain unclear. We examined whether Nrf2 regulates the transcription of Bdnf by binding to its exon I promoter. Furthermore, the role of Nrf2 and BDNF in the brain regions from mice with depression-like phenotypes was examined. Nrf2 regulated the transcription of Bdnf by binding to its exon I promoter. Activation of Nrf2 by sulforaphane (SFN) showed fast-acting antidepressant-like effects in mice by activating BDNF as well as by inhibiting the expression of its transcriptional repressors (HDAC2, mSin3A, and MeCP2) and revising abnormal synaptic transmission. In contrast, SFN did not affect the protein expression of BDNF and its transcriptional repressor proteins in the medial prefrontal cortex (mPFC) and hippocampus, nor did it reduce depression-like behaviors and abnormal synaptic transmission in Nrf2 knockout mice. In the mouse model of chronic social defeat stress (CSDS), protein levels of Nrf2 and BDNF in the mPFC and hippocampus were lower than those of control and CSDS-resilient mice. In contrast, the protein levels of BDNF transcriptional repressors in the CSDS-susceptible mice were higher than those of control and CSDS-resilient mice. These data suggest that Nrf2 activation increases the expression of Bdnf and decreases the expression of its transcriptional repressors, which result in fast-acting antidepressant-like actions. Furthermore, abnormalities in crosstalk between Nrf2 and BDNF may contribute to the resilience versus susceptibility of mice against CSDS. Nature Publishing Group UK 2021-02-24 /pmc/articles/PMC7904924/ /pubmed/33627628 http://dx.doi.org/10.1038/s41398-021-01261-6 Text en © The Author(s) 2021 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yao, Wei
Lin, Song
Su, Jin
Cao, Qianqian
Chen, Yueyue
Chen, Jiaxu
Zhang, Zhentao
Hashimoto, Kenji
Qi, Qi
Zhang, Ji-chun
Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents
title Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents
title_full Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents
title_fullStr Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents
title_full_unstemmed Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents
title_short Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents
title_sort activation of bdnf by transcription factor nrf2 contributes to antidepressant-like actions in rodents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904924/
https://www.ncbi.nlm.nih.gov/pubmed/33627628
http://dx.doi.org/10.1038/s41398-021-01261-6
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