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Tfap2b acts in GABAergic neurons to control sleep in mice

Sleep is a universal state of behavioral quiescence in both vertebrates and invertebrates that is controlled by conserved genes. We previously found that AP2 transcription factors control sleep in C. elegans, Drosophila, and mice. Heterozygous deletion of Tfap2b, one of the mammalian AP2 paralogs, r...

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Autores principales: Hu, Yang, Bringmann, Henrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10192351/
https://www.ncbi.nlm.nih.gov/pubmed/37198238
http://dx.doi.org/10.1038/s41598-023-34772-x
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author Hu, Yang
Bringmann, Henrik
author_facet Hu, Yang
Bringmann, Henrik
author_sort Hu, Yang
collection PubMed
description Sleep is a universal state of behavioral quiescence in both vertebrates and invertebrates that is controlled by conserved genes. We previously found that AP2 transcription factors control sleep in C. elegans, Drosophila, and mice. Heterozygous deletion of Tfap2b, one of the mammalian AP2 paralogs, reduces sleep in mice. The cell types and mechanisms through which Tfap2b controls sleep in mammals are, however, not known. In mice, Tfap2b acts during early embryonic stages. In this study, we used RNA-seq to measure the gene expression changes in brains of Tfap2b(−/−) embryos. Our results indicated that genes related to brain development and patterning were differentially regulated. As many sleep-promoting neurons are known to be GABAergic, we measured the expression of GAD1, GAD2 and Vgat genes in different brain areas of adult Tfap2b(+/−) mice using qPCR. These experiments suggested that GABAergic genes are downregulated in the cortex, brainstem and cerebellum areas, but upregulated in the striatum. To investigate whether Tfap2b controls sleep through GABAergic neurons, we specifically deleted Tfap2b in GABAergic neurons. We recorded the EEG and EMG before and after a 6-h period of sleep deprivation and extracted the time spent in NREM and in REM sleep as well as delta and theta power to assess NREM and REM sleep, respectively. During baseline conditions, Vgat-tfap2b(−/−) mice exhibited both shortened NREM and REM sleep time and reduced delta and theta power. Consistently, weaker delta and theta power were observed during rebound sleep in the Vgat-tfap2b(−/−) mice after sleep deprivation. Taken together, the results indicate that Tfap2b in GABAergic neurons is required for normal sleep.
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spelling pubmed-101923512023-05-19 Tfap2b acts in GABAergic neurons to control sleep in mice Hu, Yang Bringmann, Henrik Sci Rep Article Sleep is a universal state of behavioral quiescence in both vertebrates and invertebrates that is controlled by conserved genes. We previously found that AP2 transcription factors control sleep in C. elegans, Drosophila, and mice. Heterozygous deletion of Tfap2b, one of the mammalian AP2 paralogs, reduces sleep in mice. The cell types and mechanisms through which Tfap2b controls sleep in mammals are, however, not known. In mice, Tfap2b acts during early embryonic stages. In this study, we used RNA-seq to measure the gene expression changes in brains of Tfap2b(−/−) embryos. Our results indicated that genes related to brain development and patterning were differentially regulated. As many sleep-promoting neurons are known to be GABAergic, we measured the expression of GAD1, GAD2 and Vgat genes in different brain areas of adult Tfap2b(+/−) mice using qPCR. These experiments suggested that GABAergic genes are downregulated in the cortex, brainstem and cerebellum areas, but upregulated in the striatum. To investigate whether Tfap2b controls sleep through GABAergic neurons, we specifically deleted Tfap2b in GABAergic neurons. We recorded the EEG and EMG before and after a 6-h period of sleep deprivation and extracted the time spent in NREM and in REM sleep as well as delta and theta power to assess NREM and REM sleep, respectively. During baseline conditions, Vgat-tfap2b(−/−) mice exhibited both shortened NREM and REM sleep time and reduced delta and theta power. Consistently, weaker delta and theta power were observed during rebound sleep in the Vgat-tfap2b(−/−) mice after sleep deprivation. Taken together, the results indicate that Tfap2b in GABAergic neurons is required for normal sleep. Nature Publishing Group UK 2023-05-17 /pmc/articles/PMC10192351/ /pubmed/37198238 http://dx.doi.org/10.1038/s41598-023-34772-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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 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/) .
spellingShingle Article
Hu, Yang
Bringmann, Henrik
Tfap2b acts in GABAergic neurons to control sleep in mice
title Tfap2b acts in GABAergic neurons to control sleep in mice
title_full Tfap2b acts in GABAergic neurons to control sleep in mice
title_fullStr Tfap2b acts in GABAergic neurons to control sleep in mice
title_full_unstemmed Tfap2b acts in GABAergic neurons to control sleep in mice
title_short Tfap2b acts in GABAergic neurons to control sleep in mice
title_sort tfap2b acts in gabaergic neurons to control sleep in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10192351/
https://www.ncbi.nlm.nih.gov/pubmed/37198238
http://dx.doi.org/10.1038/s41598-023-34772-x
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