AUTHOR=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 

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

JOURNAL=Frontiers in Neuroscience

VOLUME=15

YEAR=2021

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.745668

DOI=10.3389/fnins.2021.745668

ISSN=1662-453X

ABSTRACT=<p>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 (<italic>p</italic> &lt; 0.05). Pathway analysis of these genes indicated that the impaired glutamatergic synapse pathway is involved in ARHL (<italic>p</italic> = 0.0038). Further gene co-expression analysis showed that the expression level of glutamine synthetase (<italic>Gls</italic>), which is significantly correlated with ARHL (<italic>n</italic> = 26, <italic>r</italic> = −0.46, <italic>p</italic> = 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.</p>