Age-related changes of gene expression associated with hearing loss and development of a drug delivery system in the inner ear

老年性听力损失是由听觉神经元和耳蜗毛细胞的变性、退变引起的，导致听觉脑干活动的改变。目的探讨幼龄和老年小鼠耳蜗、耳蜗核（CN）和下丘（IC）基因表达的变化。我们用C57B6小鼠，用听觉脑干反应测量听阈。结果表明，CN中蛋白激酶ec_ （Pkc -epsilon）和IC中谷氨酸受体嗜离子性NMDA1 （Grin1）等基因下调，CN和IC中甘氨酸氨基转移酶（Gatm）等基因上调，Pkc调节突触间隙中的神经递质，Grin1在兴奋性神经传递中起重要作用，这可能与听觉脑干活动的变化有关。这些结果为进一步利用分子生物学方法研究老年性脱发奠定了基础。下一步的研究目标是开发内耳局部给药系统。我们用了豚鼠和老鼠。采用微渗透泵和微导管对豚鼠耳蜗内地塞米松药物浓度进行了研究。研究了小鼠内耳直接输注庆大霉素的效果。

Age-related hearing loss, presbycusis is caused by degeneration and deciduation of auditory neurons and cochlear hair cells, and it results in the changes of auditory brainstem activity. We aimed to investigate the gene expression changing in the cochlea, cochlear nucleus (CN) and inferior, colliculus (IC) between young and aged mice. We used C57B6 mice and measured the hearing threshold with auditory brainstem response. The results showed that some genes were down regulated including Protein kinaseC_(PKC-epsilon) in CN and Glutamate receptor ionotropic NMDA1 (Grin1) in IC. Upregulation of several genes including glycine amidinotransferase(Gatm) was detected in CN and in IC. Pkc regulates neurotransmitters in the synaptic cleft and Grin1 has important role in excitatory neurotransmission, which may be relevant to the change in auditory brainstem activity. These results provide a foundation for further studies to Presbicusis with molecular biology.The goal of next study is to develop the local drug delivery system in the inner ear. We used guinea pigs and mice. The drug concentration (dexamethasone) of the guinea pig cochlea using mini-osmotic pump and the microcatheter was studied. The direct infusion of the mice inner ear was studied and demonstrated effective in the delivery of gentamicin.