Metabolomics Analysis Reveals Alterations in Cochlear Metabolic Profiling in Mice with Noise-Induced Hearing Loss.
Long MiaoJuan ZhangLihong YinYue-Pu PuPublished in: BioMed research international (2022)
Noise-induced hearing loss (NIHL) has always been an important occupational hazard, but the exact etiopathogenesis underlying NIHL remains unclear. Herein, we aimed to find metabolic biomarkers involved in the development of NIHL based on a mouse model using a gas chromatography coupled with mass spectrometry (GC-MS) metabolomics technique. We showed that the auditory brainstem response (ABR) thresholds at the frequencies of 4, 8, 12, 16, 24, and 32 kHz were all significantly elevated in the noise-exposed mice. Noise could cause outer hair cell (OHC) loss in the base of the cochlea. A total of 17 differential metabolites and 9 metabolic pathways were significantly affected following noise exposure. Spermidine acting as an autophagy modulator was found to be 2.85-fold higher in the noise-exposed group than in the control group and involved in β -alanine metabolism and arginine and proline metabolism pathways. Additionally, we demonstrated that LC3B and Beclin1 were expressed in the spiral ganglion neurons (SGNs), and their mRNA levels were increased after noise. We showed that SOD activity was significantly decreased in the cochlea of noise-exposed mice. Further experiments suggested that SOD1 and SOD2 proteins in the SGNs were all decreased following noise exposure. The upregulation of spermidine may induce LC3B- and Beclin1-mediated autophagy in the cochlear hair cells (HCs) through β -alanine metabolism and arginine and proline metabolism and be involved in the NIHL. ROS-mediated oxidative damage may be a pivotal molecular mechanism of NIHL. Taken together, spermidine can be regarded as an important metabolic marker for the diagnosis of NIHL.
Keyphrases
- mass spectrometry
- air pollution
- hearing loss
- gas chromatography
- mouse model
- liquid chromatography
- induced apoptosis
- signaling pathway
- endoplasmic reticulum stress
- nitric oxide
- single cell
- oxidative stress
- dna damage
- ms ms
- high resolution
- spinal cord
- spinal cord injury
- poor prognosis
- mesenchymal stem cells
- tandem mass spectrometry
- high fat diet induced
- working memory
- molecular dynamics
- skeletal muscle
- endothelial cells
- drug induced
- gas chromatography mass spectrometry
- cell therapy
- amino acid
- bone marrow
- density functional theory
- reactive oxygen species