Association between age‑related hearing loss and cognitive decline in C57BL/6J mice.

Accumulating evidence has revealed the link between age‑related hearing loss (presbycusis) and cognitive decline; however, their exact association remains unclear. The present study aimed to investigate the association between age‑related hearing loss and cognitive decline, and to explore the underlying mechanisms. Briefly, three groups of C57BL/6J mice were evaluated, based on their age, as follows: Young group, 3 months; adult group, 6 months; and middle‑aged group, 15 months. The results of an auditory brainstem response (ABR) test demonstrated that the hearing threshold levels of the mice were increased in those aged 6 and 15 months compared with those aged 3 months, thus suggesting that significant hearing loss occurred at 6 months, and worsened at 15 months. The results of a Morris water maze test demonstrated that spatial learning and memory function was significantly decreased in 15‑month‑old mice, but not in 6‑month‑old mice. Pearson analysis indicated that the escape latency was positively correlated with hearing threshold at 16 kHz and percentage of time in the target quadrant was negatively correlated with hearing threshold at 16 kHz, thus suggesting a correlation between age‑related hearing loss and cognitive decline. The auditory cortex and hippocampal CA1 region in 15‑month‑old mice exhibited significantly decreased cell numbers, abnormal arrangement and morphological alterations. Transmission electron microscopy revealed reduced synapse numbers and synaptic vesicle density in mice aged 15 months. Furthermore, the protein expression levels of matrix metalloproteinase (MMP)‑9 in the auditory cortex and hippocampus in the 15‑month‑old mice were significantly higher than in the 3‑month‑old mice. In conclusion, these findings support the correlation between age‑related hearing loss and cognitive decline in C57BL/6J mice, and indicated that MMP‑9 expression in the auditory cortex and hippocampus may be associated with the underlying mechanisms.