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The BDNF–TrkB–CREB Signalling Pathway Is Involved in Bisphenol S-Induced Neurotoxicity in Male Mice by Regulating Methylation

Bisphenol S (BPS), the most common substitute for bisphenol A in manufacturing, is associated with neurotoxicity, but its molecular mechanisms are unclear. Here, we studied the role of the BDNF–TrkB–CREB (brain-derived neurotrophic factor–tropomyosin-related kinase B–CAMP response element-binding pr...

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Autores principales: Li, Yi-Zhou, Wu, Zi-Yao, Zhu, Bi-Qi, Wang, Yu-Xiao, Kan, Ya-Qi, Zeng, Huai-Cai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331819/
https://www.ncbi.nlm.nih.gov/pubmed/35893846
http://dx.doi.org/10.3390/toxics10080413
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author Li, Yi-Zhou
Wu, Zi-Yao
Zhu, Bi-Qi
Wang, Yu-Xiao
Kan, Ya-Qi
Zeng, Huai-Cai
author_facet Li, Yi-Zhou
Wu, Zi-Yao
Zhu, Bi-Qi
Wang, Yu-Xiao
Kan, Ya-Qi
Zeng, Huai-Cai
author_sort Li, Yi-Zhou
collection PubMed
description Bisphenol S (BPS), the most common substitute for bisphenol A in manufacturing, is associated with neurotoxicity, but its molecular mechanisms are unclear. Here, we studied the role of the BDNF–TrkB–CREB (brain-derived neurotrophic factor–tropomyosin-related kinase B–CAMP response element-binding protein) signalling pathway in bisphenol S-induced neurotoxicity via methylation regulation in male C57BL/6 mice. The mice were treated with sesame oil or 2, 20 and 200 mg/kg body weight BPS for 28 consecutive days, and the hippocampus was extracted. We recorded the body weight, organ index, and hippocampal pathology and ultrastructure of the mice. The BDNF, TrkB, CREB, phosphorylated (p)-CREB, DNMTs (DNA methyltransferases) levels were determined by qRT-PCR and/or Western blotting. BDNF promoter IV methylation level was detected by bisulfite sequencing PCR. BPS damaged the mouse hippocampus ultrastructure and reduced the number of synapses. Further, it increased the methylation rate of BDNF promoter IV; downregulated BDNF, CREB, p-CREB/CREB and DNMT1 expression; and upregulated DNMT3a and DNMT3b expression. Therefore, we speculate that the BDNF–TrkB–CREB pathway may be involved in BPS-induced neurotoxicity in male mice by regulating methylation.
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spelling pubmed-93318192022-07-29 The BDNF–TrkB–CREB Signalling Pathway Is Involved in Bisphenol S-Induced Neurotoxicity in Male Mice by Regulating Methylation Li, Yi-Zhou Wu, Zi-Yao Zhu, Bi-Qi Wang, Yu-Xiao Kan, Ya-Qi Zeng, Huai-Cai Toxics Article Bisphenol S (BPS), the most common substitute for bisphenol A in manufacturing, is associated with neurotoxicity, but its molecular mechanisms are unclear. Here, we studied the role of the BDNF–TrkB–CREB (brain-derived neurotrophic factor–tropomyosin-related kinase B–CAMP response element-binding protein) signalling pathway in bisphenol S-induced neurotoxicity via methylation regulation in male C57BL/6 mice. The mice were treated with sesame oil or 2, 20 and 200 mg/kg body weight BPS for 28 consecutive days, and the hippocampus was extracted. We recorded the body weight, organ index, and hippocampal pathology and ultrastructure of the mice. The BDNF, TrkB, CREB, phosphorylated (p)-CREB, DNMTs (DNA methyltransferases) levels were determined by qRT-PCR and/or Western blotting. BDNF promoter IV methylation level was detected by bisulfite sequencing PCR. BPS damaged the mouse hippocampus ultrastructure and reduced the number of synapses. Further, it increased the methylation rate of BDNF promoter IV; downregulated BDNF, CREB, p-CREB/CREB and DNMT1 expression; and upregulated DNMT3a and DNMT3b expression. Therefore, we speculate that the BDNF–TrkB–CREB pathway may be involved in BPS-induced neurotoxicity in male mice by regulating methylation. MDPI 2022-07-23 /pmc/articles/PMC9331819/ /pubmed/35893846 http://dx.doi.org/10.3390/toxics10080413 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Yi-Zhou
Wu, Zi-Yao
Zhu, Bi-Qi
Wang, Yu-Xiao
Kan, Ya-Qi
Zeng, Huai-Cai
The BDNF–TrkB–CREB Signalling Pathway Is Involved in Bisphenol S-Induced Neurotoxicity in Male Mice by Regulating Methylation
title The BDNF–TrkB–CREB Signalling Pathway Is Involved in Bisphenol S-Induced Neurotoxicity in Male Mice by Regulating Methylation
title_full The BDNF–TrkB–CREB Signalling Pathway Is Involved in Bisphenol S-Induced Neurotoxicity in Male Mice by Regulating Methylation
title_fullStr The BDNF–TrkB–CREB Signalling Pathway Is Involved in Bisphenol S-Induced Neurotoxicity in Male Mice by Regulating Methylation
title_full_unstemmed The BDNF–TrkB–CREB Signalling Pathway Is Involved in Bisphenol S-Induced Neurotoxicity in Male Mice by Regulating Methylation
title_short The BDNF–TrkB–CREB Signalling Pathway Is Involved in Bisphenol S-Induced Neurotoxicity in Male Mice by Regulating Methylation
title_sort bdnf–trkb–creb signalling pathway is involved in bisphenol s-induced neurotoxicity in male mice by regulating methylation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331819/
https://www.ncbi.nlm.nih.gov/pubmed/35893846
http://dx.doi.org/10.3390/toxics10080413
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