Deng Tingzhi, Li Jingjing, Liu Jian, Xu Fuyi, Liu Xiaoya, Mi Jia, Bergquist Jonas, Wang Helen, Yang Chunhua, Lu Lu, Song Xicheng, Yao Cuifang, Tian Geng, Zheng Qing Yin
Precision Medicine Research Center, School of Pharmacy, Binzhou Medical University, Yantai, China.
Department of Otorhinolaryngology-Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China.
Front Neurosci. 2021 Nov 17;15:745668. doi: 10.3389/fnins.2021.745668. eCollection 2021.
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 ( < 0.05). Pathway analysis of these genes indicated that the impaired glutamatergic synapse pathway is involved in ARHL ( = 0.0038). Further gene co-expression analysis showed that the expression level of glutamine synthetase (), which is significantly correlated with ARHL ( = 26, = -0.46, = 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.
年龄相关性听力损失（ARHL）与认知功能障碍有关；然而，其详细的潜在机制仍不清楚。本研究的目的是采用系统遗传学方法探究潜在的机制。对老年（12 - 32月龄）BXD小鼠品系进行了全转录组关联研究。从56个BXD品系中获取海马体基因表达数据，并从54个BXD品系中评估听力敏锐度。进一步的相关性分析在海马体中总共鉴定出1435个与听力相关的基因（<0.05）。对这些基因的通路分析表明，受损的谷氨酸能突触通路与ARHL有关（=0.0038）。进一步的基因共表达分析表明，谷氨酰胺合成酶（）的表达水平与ARHL显著相关（=26，=-0.46，=0.0193），它是谷氨酸能突触通路中的关键调节因子，且与学习和记忆行为相关。在本研究中，我们首次对与ARHL、学习和记忆行为相关的海马体基因表达模式进行了系统评估。我们的结果提供了涉及ARHL与认知功能障碍关联的新的潜在分子机制。
