The relationship between age-related hearing loss and synaptic changes in the hippocampus of C57BL/6J mice

To explore the relationship between age-related hearing loss (presbycusis) and synaptic degeneration in the hippocampal CA3 region of C57BL/6J mice, we investigated both cognitive performance and synaptic changes within the hippocampus of C57BL/6J mice from three age groups of 6–8, 24–26, and 42–44 weeks; CBA/CaJ mice served as controls. The auditory brainstem response was used as a measure of hearing threshold, and cognitive behavior was evaluated using the Morris water maze. The ultrastructure of synapses was observed with transmission electron microscopy, and the quantity and distribution of the synaptic markers synaptophysin and PSD-95 were observed with immunohistochemistry. The hearing threshold of C57BL/6J mice was significantly higher at 24–26 weeks than at 6–8 weeks, and hearing loss was profound at 42–44 weeks. This was accompanied by progressive degeneration of synapses within the auditory cortex. In contrast, the hearing threshold of CBA/CaJ mice was relatively unchanged at 24–26 weeks of age, and these mice developed only mild hearing loss at 42–44 weeks of age. Interestingly, C57BL/6J, but not CBA/CaJ mice clearly exhibited both decreased performance in the Morris water maze and degeneration of synapses within the hippocampus. We therefore conclude that age-related hearing loss is accompanied by the degeneration of synapses in the hippocampal CA3 region of C57BL/6J mice.

Research Highlights
► In C57BL/6J mice, hearing threshold increase at 24–26 weeks old age, and by 42–44 weeks they have profound hearing loss.
► This hearing loss is coincident with degeneration of synapses within the auditory cortex.
► Spatial learning and memory are also clearly decreased at 42–44 weeks in C57BL/6J mice.
► The decrease in cognitive function is associated with synapse degeneration within the hippocampal CA3 region.
► Age-related hearing loss is accompanied by the degeneration of synapses in the hippocampal CA3 of C57BL/6J mice.