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

老年性耳聋是听觉神经元和耳蜗毛细胞变性、脱落，导致听性脑干活动改变而引起的听力损失。本研究旨在探讨青年和老年小鼠耳蜗、耳蜗核（CN）和下丘（IC）基因表达的变化。采用C57 B6小鼠，用听性脑干反应测定其听阈。结果表明，CN中的蛋白激酶C_（PKC-C）和IC中的谷氨酸受体离子型NMDA 1（Grin 1）基因表达下调。在CN和IC中检测到包括甘氨酸脒基转移酶（Gatm）在内的几个基因的上调。PKC调节突触间隙内的神经递质，Grin 1在兴奋性神经传递中起重要作用，可能与听性脑干活动的改变有关。这些结果为进一步从分子生物学角度研究老年性耳聋提供了基础，下一步的研究目标是开发内耳局部给药系统。我们用的是豚鼠和老鼠。本文研究了微渗透泵和微导管对豚鼠耳蜗药物浓度（地塞米松）的影响。研究了庆大霉素在小鼠内耳的直接输注，并证明了其在递送庆大霉素方面的有效性。

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.