Paternal nicotine exposure defines different behavior in subsequent generation via hyper-methylation of mmu-miR-15b

Abstract The neurobehavioral effects of paternal smoking and nicotine use have not been widely reported. In the present study, nicotine exposure induced depression in the paternal generation, but reduced depression and promoted hyperactivity in F1 offspring. While this intergenerational effect was n...

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Autores principales:	Jingbo Dai, Zhaoxia Wang, Wangjie Xu, Meixing Zhang, Zijue Zhu, Xianglong Zhao, Dong Zhang, Dongsheng Nie, Lianyun Wang, Zhongdong Qiao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/283c5422c4ab4114b86d90348d3fd0f8
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spelling	oai:doaj.org-article:283c5422c4ab4114b86d90348d3fd0f82021-12-02T12:31:50ZPaternal nicotine exposure defines different behavior in subsequent generation via hyper-methylation of mmu-miR-15b10.1038/s41598-017-07920-32045-2322https://doaj.org/article/283c5422c4ab4114b86d90348d3fd0f82017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07920-3https://doaj.org/toc/2045-2322Abstract The neurobehavioral effects of paternal smoking and nicotine use have not been widely reported. In the present study, nicotine exposure induced depression in the paternal generation, but reduced depression and promoted hyperactivity in F1 offspring. While this intergenerational effect was not passed down to the F2 generation. Further studies revealed that nicotine induced the down-regulation of mmu-miR-15b expression due to hyper-methylation in the CpG island shore region of mmu-miR-15b in both the spermatozoa of F0 mice and the brains of F1 mice. As the target gene of mmu-miR-15b, Wnt4 expression was elevated in the thalamus of F1 mice due to the inheritance of DNA methylation patterns from the paternal generation. Furthermore, the increased expression of Wnt4 elevated the phosphorylation level of its downstream protein GSK-3 through the canonical WNT4 pathway which involved in the behavioral alterations observed in F1 mice. Moreover, in vivo stereotaxic brain injections were used to induce the overexpression of mmu-miR-15b and WNT4 and confirm the neurobehavioral effects in vitro. The behavioral phenotype of the F1 mice resulting from paternal nicotine exposure could be attenuated by viral manipulation of mmu-miR-15b in the thalamus.Jingbo DaiZhaoxia WangWangjie XuMeixing ZhangZijue ZhuXianglong ZhaoDong ZhangDongsheng NieLianyun WangZhongdong QiaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jingbo Dai Zhaoxia Wang Wangjie Xu Meixing Zhang Zijue Zhu Xianglong Zhao Dong Zhang Dongsheng Nie Lianyun Wang Zhongdong Qiao Paternal nicotine exposure defines different behavior in subsequent generation via hyper-methylation of mmu-miR-15b
description	Abstract The neurobehavioral effects of paternal smoking and nicotine use have not been widely reported. In the present study, nicotine exposure induced depression in the paternal generation, but reduced depression and promoted hyperactivity in F1 offspring. While this intergenerational effect was not passed down to the F2 generation. Further studies revealed that nicotine induced the down-regulation of mmu-miR-15b expression due to hyper-methylation in the CpG island shore region of mmu-miR-15b in both the spermatozoa of F0 mice and the brains of F1 mice. As the target gene of mmu-miR-15b, Wnt4 expression was elevated in the thalamus of F1 mice due to the inheritance of DNA methylation patterns from the paternal generation. Furthermore, the increased expression of Wnt4 elevated the phosphorylation level of its downstream protein GSK-3 through the canonical WNT4 pathway which involved in the behavioral alterations observed in F1 mice. Moreover, in vivo stereotaxic brain injections were used to induce the overexpression of mmu-miR-15b and WNT4 and confirm the neurobehavioral effects in vitro. The behavioral phenotype of the F1 mice resulting from paternal nicotine exposure could be attenuated by viral manipulation of mmu-miR-15b in the thalamus.
format	article
author	Jingbo Dai Zhaoxia Wang Wangjie Xu Meixing Zhang Zijue Zhu Xianglong Zhao Dong Zhang Dongsheng Nie Lianyun Wang Zhongdong Qiao
author_facet	Jingbo Dai Zhaoxia Wang Wangjie Xu Meixing Zhang Zijue Zhu Xianglong Zhao Dong Zhang Dongsheng Nie Lianyun Wang Zhongdong Qiao
author_sort	Jingbo Dai
title	Paternal nicotine exposure defines different behavior in subsequent generation via hyper-methylation of mmu-miR-15b
title_short	Paternal nicotine exposure defines different behavior in subsequent generation via hyper-methylation of mmu-miR-15b
title_full	Paternal nicotine exposure defines different behavior in subsequent generation via hyper-methylation of mmu-miR-15b
title_fullStr	Paternal nicotine exposure defines different behavior in subsequent generation via hyper-methylation of mmu-miR-15b
title_full_unstemmed	Paternal nicotine exposure defines different behavior in subsequent generation via hyper-methylation of mmu-miR-15b
title_sort	paternal nicotine exposure defines different behavior in subsequent generation via hyper-methylation of mmu-mir-15b
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/283c5422c4ab4114b86d90348d3fd0f8
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Paternal nicotine exposure defines different behavior in subsequent generation via hyper-methylation of mmu-miR-15b

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