Frontiers in Neuroscience (Nov 2021)

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

  • 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

DOI
https://doi.org/10.3389/fnins.2021.745668
Journal volume & issue
Vol. 15

Abstract

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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.

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