Background:
Noise-induced hearing loss (NIHL) arises from acute or prolonged exposure to loud sounds. Early diagnosis is challenging because some individuals may not exhibit significant threshold shifts on standard audiometry, despite underlying molecular changes. Detecting such changes could enable earlier intervention and therapy development. Proteomic analysis provides a powerful approach to capture alterations in protein expression that reflect physiological states. This study investigated the proteome of perilymph, cerebrospinal fluid (CSF), whole blood, and plasma in Sprague–Dawley rats to identify biomarkers and pathways associated with NIHL.
Methods:
Rats were exposed to acute noise (110 dB, 1 h) under anaesthesia, resulting in a ~30 dB click-evoked threshold shift, measured via cochlear nerve Compound Action Potentials (CAPs). Proteins from perilymph, CSF, blood, and plasma were analysed by LC–MS/MS in data-independent acquisition (DIA) mode. Differential expression analysis (DEA) was conducted using the Mass Spectrometry Downstream Analysis Pipeline (MS-DAP) with DEqMS, MSqRob, and MS-EmpiRe statistical models. Proteins identified as significant in at least two models were considered robust. Overlap between local (perilymph, CSF) and systemic (blood, plasma) proteins was examined to identify common molecular responses to noise trauma. All procedures were approved by the Macquarie University Animal Ethics Committee (AEC No. 2023/001).
Results:
Findings demonstrated that MS-DAP detected 1,033 proteins in perilymph, 1,305 in CSF, 2,152 in blood, and 396 in plasma in 6 animals. Using two statistical models (MSqRob and MS-EmpiRe), DEA revealed 2 significant proteins in perilymph, 29 in CSF, 90 in blood, and 5 in plasma. The Ig gamma-1 chain C region (IGHG1) was consistently upregulated, showing a ~3-fold increase in perilymph and a ~2-fold increase in plasma. This overlap suggests a systemic immune response to noise trauma and highlights the potential of blood-based biomarkers for studying NIHL.
Conclusion:
This study demonstrates that acute noise exposure induces proteomic changes detectable in both local and systemic fluids, with IGHG1 emerging as a potential biomarker linking cochlear and systemic responses. These findings support the feasibility of using accessible blood samples to study molecular pathways of NIHL. Future work will extend to chronic models to better define biomarker signatures and functional outcomes.