Noise exposure induces microglial reactivity and context-dependent cognitive vulnerability in chronic noise-induced hearing loss rats.

This study investigated whether chronic noise-induced hearing loss (NIHL) alters cognitive performance during acute noise exposure and examined associated microglial changes in the auditory cortex (ACx) and hippocampus (HC). Sprague-Dawley rats were exposed to broadband white noise (2-20 kHz, 115 dB SPL, 3 h per day for 5 days) to induce NIHL. Cognitive function was evaluated using the novel object recognition test and Y-maze test across three conditions: pre-, post-, and post with sound (w/ S)-phases. Microglial activation was assessed via Iba1 immunofluorescence, Sholl analysis, and Iba1-brevican (BCAN) co-localization. Hippocampal neuroinflammation and autophagy were measured using western blotting for ATG5, TNF-α, and IL-6, as well as qRT-PCR for CD68, IRF1, and IL-1β in MACS-isolated microglia. NIHL increased the discrimination index (DI) in the post-phase. However, DI significantly decreased during acute noise exposure, which was accompanied by increased exploration of the familiar object. Iba1 expression was elevated in both ACx and HC after acute noise exposure, with greater upregulation observed in the NIHL w/ S group. Hippocampal microglia in NIHL w/ S displayed enlarged somata and reduced process complexity. In the ACx, Iba1-BCAN co-localization progressively increased. NIHL reduced hippocampal ATG5 and increased TNF-α levels in the NIHL group, while CD68 and IRF1 expression were further elevated in NIHL w/ S microglia. Chronic NIHL induces context-dependent cognitive vulnerability that becomes apparent under acoustic challenge rather than at baseline. Collectively, these results suggest that hippocampal microglial sensitization may underlie the noise-induced cognitive changes associated with chronic hearing loss.