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.