Department of Otology & Skull Base Surgery, Eye Ear Nose & Throat Hospital, Fudan University, Shanghai 200031, China.
Exp Gerontol. 2011 Sep;46(9):716-22. doi: 10.1016/j.exger.2011.04.007. Epub 2011 May 14.
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.
为了探索年龄相关性听力损失(老年性聋)与海马 CA3 区突触退化之间的关系,我们研究了来自三个年龄组的 C57BL/6J 小鼠(6-8 周、24-26 周和 42-44 周)和 CBA/CaJ 小鼠的认知表现和海马内突触变化。听觉脑干反应用于测量听力阈值,而 Morris 水迷宫用于评估认知行为。用透射电子显微镜观察突触的超微结构,用免疫组织化学观察突触标志物突触小泡蛋白和 PSD-95 的数量和分布。C57BL/6J 小鼠在 24-26 周时的听力阈值明显高于 6-8 周时,而在 42-44 周时听力损失严重。这伴随着听觉皮层内突触的进行性退化。相比之下,CBA/CaJ 小鼠在 24-26 周时的听力阈值相对不变,而在 42-44 周时仅出现轻度听力损失。有趣的是,C57BL/6J 小鼠但不是 CBA/CaJ 小鼠明显表现出 Morris 水迷宫中的表现下降和海马内突触的退化。因此,我们得出结论,年龄相关性听力损失伴随着 C57BL/6J 小鼠海马 CA3 区突触的退化。