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Chronic corticosterone disrupts the circadian rhythm of CRH expression and m(6)A RNA methylation in the chicken hypothalamus

BACKGROUND: Corticotropin-releasing hormone (CRH), the major secretagogue of the hypothalamic-pituitary-adrenal (HPA) axis, is intricately intertwined with the clock genes to regulate the circadian rhythm of various body functions. N6-methyladenosine (m(6)A) RNA methylation is involved in the regula...

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Autores principales: Yang, Yang, Han, Wanwan, Zhang, Aijia, Zhao, Mindie, Cong, Wei, Jia, Yimin, Wang, Deyun, Zhao, Ruqian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8902767/
https://www.ncbi.nlm.nih.gov/pubmed/35255992
http://dx.doi.org/10.1186/s40104-022-00677-4
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author Yang, Yang
Han, Wanwan
Zhang, Aijia
Zhao, Mindie
Cong, Wei
Jia, Yimin
Wang, Deyun
Zhao, Ruqian
author_facet Yang, Yang
Han, Wanwan
Zhang, Aijia
Zhao, Mindie
Cong, Wei
Jia, Yimin
Wang, Deyun
Zhao, Ruqian
author_sort Yang, Yang
collection PubMed
description BACKGROUND: Corticotropin-releasing hormone (CRH), the major secretagogue of the hypothalamic-pituitary-adrenal (HPA) axis, is intricately intertwined with the clock genes to regulate the circadian rhythm of various body functions. N6-methyladenosine (m(6)A) RNA methylation is involved in the regulation of circadian rhythm, yet it remains unknown whether CRH expression and m(6)A modification oscillate with the clock genes in chicken hypothalamus and how the circadian rhythms change under chronic stress. RESULTS: Chronic exposure to corticosterone (CORT) eliminated the diurnal patterns of plasma CORT and melatonin levels in the chicken. The circadian rhythms of clock genes in hippocampus, hypothalamus and pituitary are all disturbed to different extent in CORT-treated chickens. The most striking changes occur in hypothalamus in which the diurnal fluctuation of CRH mRNA is flattened, together with mRNA of other feeding-related neuropeptides. Interestingly, hypothalamic m(6)A level oscillates in an opposite pattern to CRH mRNA, with lowest m(6)A level after midnight (ZT18) corresponding to the peak of CRH mRNA before dawn (ZT22). CORT diminished the circadian rhythm of m(6)A methylation with significantly increased level at night. Further site-specific m(6)A analysis on 3’UTR of CRH mRNA indicates that higher m(6)A on 3’UTR of CRH mRNA coincides with lower CRH mRNA at night (ZT18 and ZT22). CONCLUSIONS: Our results indicate that chronic stress disrupts the circadian rhythms of CRH expression in hypothalamus, leading to dysfunction of HPA axis in the chicken. RNA m(6)A modification is involved in the regulation of circadian rhythms in chicken hypothalamus under both basal and chronic stress conditions. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40104-022-00677-4.
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spelling pubmed-89027672022-03-18 Chronic corticosterone disrupts the circadian rhythm of CRH expression and m(6)A RNA methylation in the chicken hypothalamus Yang, Yang Han, Wanwan Zhang, Aijia Zhao, Mindie Cong, Wei Jia, Yimin Wang, Deyun Zhao, Ruqian J Anim Sci Biotechnol Research BACKGROUND: Corticotropin-releasing hormone (CRH), the major secretagogue of the hypothalamic-pituitary-adrenal (HPA) axis, is intricately intertwined with the clock genes to regulate the circadian rhythm of various body functions. N6-methyladenosine (m(6)A) RNA methylation is involved in the regulation of circadian rhythm, yet it remains unknown whether CRH expression and m(6)A modification oscillate with the clock genes in chicken hypothalamus and how the circadian rhythms change under chronic stress. RESULTS: Chronic exposure to corticosterone (CORT) eliminated the diurnal patterns of plasma CORT and melatonin levels in the chicken. The circadian rhythms of clock genes in hippocampus, hypothalamus and pituitary are all disturbed to different extent in CORT-treated chickens. The most striking changes occur in hypothalamus in which the diurnal fluctuation of CRH mRNA is flattened, together with mRNA of other feeding-related neuropeptides. Interestingly, hypothalamic m(6)A level oscillates in an opposite pattern to CRH mRNA, with lowest m(6)A level after midnight (ZT18) corresponding to the peak of CRH mRNA before dawn (ZT22). CORT diminished the circadian rhythm of m(6)A methylation with significantly increased level at night. Further site-specific m(6)A analysis on 3’UTR of CRH mRNA indicates that higher m(6)A on 3’UTR of CRH mRNA coincides with lower CRH mRNA at night (ZT18 and ZT22). CONCLUSIONS: Our results indicate that chronic stress disrupts the circadian rhythms of CRH expression in hypothalamus, leading to dysfunction of HPA axis in the chicken. RNA m(6)A modification is involved in the regulation of circadian rhythms in chicken hypothalamus under both basal and chronic stress conditions. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40104-022-00677-4. BioMed Central 2022-03-08 /pmc/articles/PMC8902767/ /pubmed/35255992 http://dx.doi.org/10.1186/s40104-022-00677-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yang, Yang
Han, Wanwan
Zhang, Aijia
Zhao, Mindie
Cong, Wei
Jia, Yimin
Wang, Deyun
Zhao, Ruqian
Chronic corticosterone disrupts the circadian rhythm of CRH expression and m(6)A RNA methylation in the chicken hypothalamus
title Chronic corticosterone disrupts the circadian rhythm of CRH expression and m(6)A RNA methylation in the chicken hypothalamus
title_full Chronic corticosterone disrupts the circadian rhythm of CRH expression and m(6)A RNA methylation in the chicken hypothalamus
title_fullStr Chronic corticosterone disrupts the circadian rhythm of CRH expression and m(6)A RNA methylation in the chicken hypothalamus
title_full_unstemmed Chronic corticosterone disrupts the circadian rhythm of CRH expression and m(6)A RNA methylation in the chicken hypothalamus
title_short Chronic corticosterone disrupts the circadian rhythm of CRH expression and m(6)A RNA methylation in the chicken hypothalamus
title_sort chronic corticosterone disrupts the circadian rhythm of crh expression and m(6)a rna methylation in the chicken hypothalamus
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8902767/
https://www.ncbi.nlm.nih.gov/pubmed/35255992
http://dx.doi.org/10.1186/s40104-022-00677-4
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