Hippocampal Transcriptome-Wide Association Study Reveals Correlations Between Impaired Glutamatergic Synapse Pathway and Age-Related Hearing Loss in BXD-Recombinant Inbred Mice

Age-related hearing loss (ARHL) is associated with cognitive dysfunction; however, the detailed underlying mechanisms remain unclear. The aim of this study is to investigate the potential underlying mechanism with a system genetics approach. A transcriptome-wide association study was performed on ag...

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Autores principales:	Tingzhi Deng, Jingjing Li, Jian Liu, Fuyi Xu, Xiaoya Liu, Jia Mi, Jonas Bergquist, Helen Wang, Chunhua Yang, Lu Lu, Xicheng Song, Cuifang Yao, Geng Tian, Qing Yin Zheng
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	hearing loss systems genetics cognitive dysfunction glutamine synthetase (Gls) gene network BXD mice strain Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/985930250b8d416bb364fea12288c929
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spelling	oai:doaj.org-article:985930250b8d416bb364fea12288c9292021-11-17T15:03:15ZHippocampal Transcriptome-Wide Association Study Reveals Correlations Between Impaired Glutamatergic Synapse Pathway and Age-Related Hearing Loss in BXD-Recombinant Inbred Mice1662-453X10.3389/fnins.2021.745668https://doaj.org/article/985930250b8d416bb364fea12288c9292021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnins.2021.745668/fullhttps://doaj.org/toc/1662-453XAge-related hearing loss (ARHL) is associated with cognitive dysfunction; however, the detailed underlying mechanisms remain unclear. The aim of this study is to investigate the potential underlying mechanism with a system genetics approach. A transcriptome-wide association study was performed on aged (12–32 months old) BXD mice strains. The hippocampus gene expression was obtained from 56 BXD strains, and the hearing acuity was assessed from 54 BXD strains. Further correlation analysis identified a total of 1,435 hearing-related genes in the hippocampus (p < 0.05). Pathway analysis of these genes indicated that the impaired glutamatergic synapse pathway is involved in ARHL (p = 0.0038). Further gene co-expression analysis showed that the expression level of glutamine synthetase (Gls), which is significantly correlated with ARHL (n = 26, r = −0.46, p = 0.0193), is a crucial regulator in glutamatergic synapse pathway and associated with learning and memory behavior. In this study, we present the first systematic evaluation of hippocampus gene expression pattern associated with ARHL, learning, and memory behavior. Our results provide novel potential molecular mechanisms involved in ARHL and cognitive dysfunction association.Tingzhi DengJingjing LiJingjing LiJingjing LiJian LiuFuyi XuFuyi XuXiaoya LiuJia MiJonas BergquistJonas BergquistHelen WangChunhua YangLu LuXicheng SongCuifang YaoGeng TianQing Yin ZhengFrontiers Media S.A.articlehearing losssystems geneticscognitive dysfunctionglutamine synthetase (Gls)gene networkBXD mice strainNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hearing loss systems genetics cognitive dysfunction glutamine synthetase (Gls) gene network BXD mice strain Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	hearing loss systems genetics cognitive dysfunction glutamine synthetase (Gls) gene network BXD mice strain Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Tingzhi Deng Jingjing Li Jingjing Li Jingjing Li Jian Liu Fuyi Xu Fuyi Xu Xiaoya Liu Jia Mi Jonas Bergquist Jonas Bergquist Helen Wang Chunhua Yang Lu Lu Xicheng Song Cuifang Yao Geng Tian Qing Yin Zheng Hippocampal Transcriptome-Wide Association Study Reveals Correlations Between Impaired Glutamatergic Synapse Pathway and Age-Related Hearing Loss in BXD-Recombinant Inbred Mice
description	Age-related hearing loss (ARHL) is associated with cognitive dysfunction; however, the detailed underlying mechanisms remain unclear. The aim of this study is to investigate the potential underlying mechanism with a system genetics approach. A transcriptome-wide association study was performed on aged (12–32 months old) BXD mice strains. The hippocampus gene expression was obtained from 56 BXD strains, and the hearing acuity was assessed from 54 BXD strains. Further correlation analysis identified a total of 1,435 hearing-related genes in the hippocampus (p < 0.05). Pathway analysis of these genes indicated that the impaired glutamatergic synapse pathway is involved in ARHL (p = 0.0038). Further gene co-expression analysis showed that the expression level of glutamine synthetase (Gls), which is significantly correlated with ARHL (n = 26, r = −0.46, p = 0.0193), is a crucial regulator in glutamatergic synapse pathway and associated with learning and memory behavior. In this study, we present the first systematic evaluation of hippocampus gene expression pattern associated with ARHL, learning, and memory behavior. Our results provide novel potential molecular mechanisms involved in ARHL and cognitive dysfunction association.
format	article
author	Tingzhi Deng Jingjing Li Jingjing Li Jingjing Li Jian Liu Fuyi Xu Fuyi Xu Xiaoya Liu Jia Mi Jonas Bergquist Jonas Bergquist Helen Wang Chunhua Yang Lu Lu Xicheng Song Cuifang Yao Geng Tian Qing Yin Zheng
author_facet	Tingzhi Deng Jingjing Li Jingjing Li Jingjing Li Jian Liu Fuyi Xu Fuyi Xu Xiaoya Liu Jia Mi Jonas Bergquist Jonas Bergquist Helen Wang Chunhua Yang Lu Lu Xicheng Song Cuifang Yao Geng Tian Qing Yin Zheng
author_sort	Tingzhi Deng
title	Hippocampal Transcriptome-Wide Association Study Reveals Correlations Between Impaired Glutamatergic Synapse Pathway and Age-Related Hearing Loss in BXD-Recombinant Inbred Mice
title_short	Hippocampal Transcriptome-Wide Association Study Reveals Correlations Between Impaired Glutamatergic Synapse Pathway and Age-Related Hearing Loss in BXD-Recombinant Inbred Mice
title_full	Hippocampal Transcriptome-Wide Association Study Reveals Correlations Between Impaired Glutamatergic Synapse Pathway and Age-Related Hearing Loss in BXD-Recombinant Inbred Mice
title_fullStr	Hippocampal Transcriptome-Wide Association Study Reveals Correlations Between Impaired Glutamatergic Synapse Pathway and Age-Related Hearing Loss in BXD-Recombinant Inbred Mice
title_full_unstemmed	Hippocampal Transcriptome-Wide Association Study Reveals Correlations Between Impaired Glutamatergic Synapse Pathway and Age-Related Hearing Loss in BXD-Recombinant Inbred Mice
title_sort	hippocampal transcriptome-wide association study reveals correlations between impaired glutamatergic synapse pathway and age-related hearing loss in bxd-recombinant inbred mice
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/985930250b8d416bb364fea12288c929
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Hippocampal Transcriptome-Wide Association Study Reveals Correlations Between Impaired Glutamatergic Synapse Pathway and Age-Related Hearing Loss in BXD-Recombinant Inbred Mice

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