Abstract
Animal-based studies have provided important insights into the structural and functional consequences of noise exposure on the cochlea. Yet, less is known about the molecular mechanisms by which noise induces cochlear damage, particularly at relatively low exposure levels. While there is ample evidence that noise exposure leads to changes in inner ear metabolism, the specific effects of noise exposure on the cochlear metabolome are poorly understood. In this study we applied liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS)-based metabolomics to analyze the effects of noise on the mouse inner ear. Mice were exposed to noise that induces temporary threshold shifts, synaptopathy and permanent hidden hearing loss. Inner ears were harvested immediately after exposure and analyzed by targeted metabolomics for the relative abundance of 220 metabolites across the major metabolic pathways in central carbon metabolism. We identified 40 metabolites differentially affected by noise. Our approach detected novel noise-modulated metabolites and pathways, as well as some already linked to noise exposure or cochlear function such as neurotransmission and oxidative stress. Furthermore, it showed that metabolic effects of noise on the inner ear depend on the intensity and duration of exposure. Collectively, our results illustrate that metabolomics provides a powerful approach for the characterization of inner ear metabolites affected by auditory trauma. This type of information could lead to the identification of drug targets and novel therapies for noise-induced hearing loss.
Highlights
Noise-induced hearing loss (NIHL) affects more than 300 million people worldwide, and 10% of the world’s population is exposed to potentially damaging sounds on a daily basis[1], making noise exposure one of the most common causes of sensorineural hearing loss
Our results show that metabolomics profiling is a powerful approach for the characterization of inner ear metabolites in normal and pathological states
We found that noise exposure induces consistent and significant metabolic changes on an acute time scale
Summary
Noise-induced hearing loss (NIHL) affects more than 300 million people worldwide, and 10% of the world’s population is exposed to potentially damaging sounds on a daily basis[1], making noise exposure one of the most common causes of sensorineural hearing loss. Loud sounds might cause a permanent threshold shift, i.e. overt hearing loss (OHL), which has traditionally been well investigated in patients and animals In this case, a broad set of structures in the cochlea can be damaged, including stereocilia, hair cells, supporting cells and even the tectorial membrane[2]. Our results identified several metabolites and pathways influenced by noise, including some already linked to exposure or cochlear function, e.g. glutamate and NAD+, as well as numerous metabolites that have not been reported previously This approach shows that the effects of noise on the inner ear metabolome depend on the intensity and duration of the exposure. This information would be helpful in guiding the design of new therapeutic approaches
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