Abstract
Acoustic trauma is the most common cause of hearing loss and tinnitus in humans. However, the impact of acoustic trauma on system biology is not fully understood. It has been increasingly recognized that tinnitus caused by acoustic trauma is unlikely to be generated by a single pathological source, but rather a complex network of changes involving not only the auditory system but also systems related to memory, emotion and stress. One obvious and significant gap in tinnitus research is a lack of biomarkers that reflect the consequences of this interactive “tinnitus-causing” network. In this study, we made the first attempt to analyse brain metabolic changes in rats following acoustic trauma using metabolomics, as a pilot study prior to directly linking metabolic changes to tinnitus. Metabolites in 12 different brain regions collected from either sham or acoustic trauma animals were profiled using a gas chromatography mass spectrometry (GC/MS)-based metabolomics platform. After deconvolution of mass spectra and identification of the molecules, the metabolomic data were processed using multivariate statistical analysis. Principal component analysis showed that metabolic patterns varied among different brain regions; however, brain regions with similar functions had a similar metabolite composition. Acoustic trauma did not change the metabolite clusters in these regions. When analyzed within each brain region using the orthogonal projection to latent structures discriminant analysis sub-model, 17 molecules showed distinct separation between control and acoustic trauma groups in the auditory cortex, inferior colliculus, superior colliculus, vestibular nucleus complex (VNC), and cerebellum. Further metabolic pathway impact analysis and the enrichment overview with network analysis suggested the primary involvement of amino acid metabolism, including the alanine, aspartate and glutamate metabolic pathways, the arginine and proline metabolic pathways and the purine metabolic pathway. Our results provide the first metabolomics evidence that acoustic trauma can induce changes in multiple metabolic pathways. This pilot study also suggests that the metabolomic approach has the potential to identify acoustic trauma-specific metabolic shifts in future studies where metabolic changes are correlated with the animal's tinnitus status.
Highlights
Acoustic trauma is the most common cause of hearing loss and tinnitus in humans (Cooper, 1994)
We did not test the animal’s auditory brainstem-evoked response (ABR) thresholds at 6 months post-exposure prior to sacrificing the animals in this study, we reported in a separate study that ABR thresholds in the exposed ear returned to the same level as that in sham animals at 6 months after exposure (Zheng et al, 2015)
gas chromatography mass spectrometry (GC/mass spectrometry (MS)) analysis of the brain tissue extracts revealed a large number of peaks (Figure 1)
Summary
Acoustic trauma is the most common cause of hearing loss and tinnitus in humans (Cooper, 1994). Using tinnitus as an example, this phantom sound is severe enough in 1% of adults to affect their day-to-day normal life (Vio and Holme, 2005). In severe cases, it can be extremely disturbing, and even lead to suicide (Shargorodsky et al, 2010). While the prevalence of tinnitus normally increases with age, noise exposure is believed to be the most common cause of tinnitus in humans (Cooper, 1994).The prevalence of tinnitus is increased by several-fold among military populations, especially those who have served in battle zones (Shah et al, 2014). It is alarming that an increasing number of adolescents and young adults are experiencing tinnitus due to risky music-listening behaviors (Vogel et al, 2014)
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