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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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.745668/full |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T08:25:24Z |
| format | Article |
| id | doaj.art-985930250b8d416bb364fea12288c929 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-19T08:25:24Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-985930250b8d416bb364fea12288c9292022-12-21T20:29:18ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-11-011510.3389/fnins.2021.745668745668Hippocampal Transcriptome-Wide Association Study Reveals Correlations Between Impaired Glutamatergic Synapse Pathway and Age-Related Hearing Loss in BXD-Recombinant Inbred MiceTingzhi Deng0Jingjing Li1Jingjing Li2Jingjing Li3Jian Liu4Fuyi Xu5Fuyi Xu6Xiaoya Liu7Jia Mi8Jonas Bergquist9Jonas Bergquist10Helen Wang11Chunhua Yang12Lu Lu13Xicheng Song14Cuifang Yao15Geng Tian16Qing Yin Zheng17Precision Medicine Research Center, School of Pharmacy, Binzhou Medical University, Yantai, ChinaPrecision Medicine Research Center, School of Pharmacy, Binzhou Medical University, Yantai, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, ChinaSecond Clinical Medical College, Binzhou Medical University, Yantai, ChinaDepartment of Plastic Surgery, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, ChinaPrecision Medicine Research Center, School of Pharmacy, Binzhou Medical University, Yantai, ChinaDepartment of Genetics, Genomics and Informatics, The University of Tennessee Health Science Center, Memphis, TN, United StatesPrecision Medicine Research Center, School of Pharmacy, Binzhou Medical University, Yantai, ChinaPrecision Medicine Research Center, School of Pharmacy, Binzhou Medical University, Yantai, ChinaPrecision Medicine Research Center, School of Pharmacy, Binzhou Medical University, Yantai, ChinaDepartment of Chemistry—BMC, Analytical Chemistry and Neurochemistry, Uppsala University, Uppsala, SwedenDepartment of Medical Biochemistry and Microbiology, BMC, Uppsala University, Uppsala, SwedenPrecision Medicine Research Center, School of Pharmacy, Binzhou Medical University, Yantai, ChinaDepartment of Genetics, Genomics and Informatics, The University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Otorhinolaryngology-Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, ChinaPrecision Medicine Research Center, School of Pharmacy, Binzhou Medical University, Yantai, ChinaPrecision Medicine Research Center, School of Pharmacy, Binzhou Medical University, Yantai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Case Western Reserve University, Cleveland, OH, United StatesAge-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.https://www.frontiersin.org/articles/10.3389/fnins.2021.745668/fullhearing losssystems geneticscognitive dysfunctionglutamine synthetase (Gls)gene networkBXD mice strain |
| spellingShingle | 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 Frontiers in Neuroscience hearing loss systems genetics cognitive dysfunction glutamine synthetase (Gls) gene network BXD mice strain |
| title | 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_short | 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 |
| topic | hearing loss systems genetics cognitive dysfunction glutamine synthetase (Gls) gene network BXD mice strain |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.745668/full |
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