Relationship Between Age-related Hearing Loss And Synaptic Changes In The Hippocampus Of C57BL/6J Mice

Objectives:To explore the relationship between age-related hearing loss and degeneration of cognition in C57BL/6J mice, we observed the hearing in ABR and their performance in the Morris water maze, CBA/CaJ mice as a control group because it could keep good hearing with age during 12 months old.To explore the relationship between age-related hearing loss and degeneration of synapse of hippocampus CA3 in C57BL/6J mice, we observed the changes in synapses of auditory and hippocampus CA3. We used some methods including the expression of synapse proteins and the ultrastructure of synapses in transmission electron microscope. We also observed the neurons and the dendritic branchings wirh Golgi staining in hippocampus CA3.To understand the change of the whole brain in C57BL/6J mice and to exclude the impaction of visual system, visual cortex as a control versus hippocampus.MethodsMale C57BL/6J mice were divided into three groups according to age:6-8 weeks old,24-26 weeks old, and 42-44 weeks old (n=10 each). Male CBA/CaJ mice were used as controls (n=9 each). The auditory brainstem response was measured to evaluate the hearing threshold. Cognitive behavior was evaluated with the Morris water maze. The quantity and distribution of synapses were determined by synaptophysin staining, and PSD-95 localization was observed with immunohistochemistry. The ultrastructure of synapses was observed with transmission electron microscopy. The neurons and the dendritic branchings of hippocampus CA3 were observed with Golgi staining.Results:The hearing threshold of C57BL/6J mice increased significantly until 24-26 weeks of age, and then mice developed profound hearing loss by 42-44 weeks of age. The hearing threshold of CBA/CaJ mice was almost normal at 24-26 weeks of age as well, only developed a mild hearing loss at 42-44 weeks of age. The degeneration of auditory cortex synapses began at 24-26 weeks, then decreased seriously at 42-44weeks in C57BL/6J, not in CBA/CaJ. There is no obvious degeneration in synaptic ultrastructure and synaptic-related proteins in visual cortex. Interestingly, decreases in performance in the Morris water maze and decreases in dendritic branching, PSD-95 expression and ultrastructure in C57BL/6J mice hippocampus CA3 were clearly observed at 42-44 weeks of age, but this was not seen in CBA/CaJ mice.Conclusions:We therefore concluded that the age-related hearing loss contributed to the degeneration of cognition and synapses in the hippocampus CA3 of C57BL/6J mice. Hearing might be the main factor.