Overexpression of the receptor for advanced glycation end-products in the auditory cortex of rats with noise-induced hearing loss

BACKGROUND: The receptor for advanced glycation end-products (RAGE) is involved in neuroinflammation. This study investigated the changes in RAGE expression following noise-induced hearing loss. METHODS: Three-week-old female SpragueDawley rats were exposed to 115 dB SPL white noise for 4 h daily for 3 d (noise group, n=16). In parallel, age and sex-matched control rats were raised under standard conditions without noise exposure (control group, n=16). After 2 h (noise immediate, n=8) and 4 wk (noise 4-week, n=8) of noise exposure, the auditory cortex was harvested and cytoplasmic and nuclear fractions were isolated. The gene expression levels of tumor necrosis factor alpha (TNF-), interleukin 6 (IL6), interleukin 1 beta (IL1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B), and RAGE were evaluated using real-time reverse transcription polymerase chain reaction. The protein expression levels of nuclear RAGE and cytosolic RAGE were evaluated using western blotting. Additionally, matrix metalloproteinase 9 (MMP9) was pharmacologically inhibited in the noise immediate group, and then nuclear and cytosolic RAGE expression levels were evaluated. RESULTS: The noise immediate and noise 4-week groups exhibited increased auditory thresholds at 4, 8, 16, and 32 kHz frequencies. The genes encoding the pro-inflammatory cytokines TNF-, IL6, IL1, and NF- B were increased 3.74, 1.63, 6.42, and 6.23-fold in the noise immediate group, respectively (P=0.047, 0.043, 0.044, and 0.041). RAGE mRNA expression was elevated 1.42-fold in the noise 4-week group (P=0.032). Cytosolic RAGE expression was increased 1.76 and 6.99-fold in the noise immediate and noise 4-week groups, respectively (P=0.04 and 0.03). Nuclear RAGE expression was comparable between the noise and control groups. matrix metalloproteinase 9 (MMP9) inhibition reduced cytosolic RAGE expression in the noise immediate group (P=0.004). CONCLUSIONS: Noise exposure increased the expression of cytosolic RAGE in the auditory cortex and upregulated pro-inflammatory genes, but this response could be alleviated by MMP9 inhibition. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12868-021-00642-3.