Bauer C A, Brozoski T J, Holder T M, Caspary D M
Southern Illinois University School of Medicine, Springfield, IL 62794-9662, USA.
Hear Res. 2000 Sep;147(1-2):175-82. doi: 10.1016/s0378-5955(00)00130-1.
It is well accepted that salicylate ototoxicity results in reversible tinnitus in humans. Salicylate-induced tinnitus may be an example of plasticity of the central auditory system and could potentially serve as a model to further understand mechanisms of tinnitus generation. This study examined levels of glutamic acid decarboxylase (GAD) and the binding characteristics of the GABA(A) receptor in auditory brainstem structures of Long-Evans rats chronically treated with salicylate. Western blotting revealed a significant 63% (P<0.008) elevation of GAD levels in the inferior colliculus (IC) of salicylate-treated subjects. This occurred in subjects demonstrating behavioral evidence of tinnitus. Muscimol saturation analysis was indicative of a salicylate-related increase in receptor affinity. Linear regression of [(3)H]muscimol saturation analysis data revealed a significant (P<0.05) reduction in K(d) values in whole IC (-48%), as well as in the central nucleus of IC (CIC, -58%) and combined external and dorsal cortex of IC (E/DCIC, -46%). The number of GABA(A) binding sites (B(max)) were also significantly (P<0.05) decreased. These changes were observed only in central auditory structures. This suggests that GAD expression and GABA(A) receptor binding characteristics may be altered with chronic exposure to sodium salicylate and these changes may represent aberrant plasticity clinically experienced as tinnitus.
水杨酸酯耳毒性会导致人类出现可逆性耳鸣，这一点已得到广泛认可。水杨酸酯诱发的耳鸣可能是中枢听觉系统可塑性的一个例子，并且有可能作为一个模型来进一步理解耳鸣产生的机制。本研究检测了长期接受水杨酸酯治疗的Long-Evans大鼠听觉脑干结构中谷氨酸脱羧酶（GAD）的水平以及GABA(A)受体的结合特性。蛋白质印迹法显示，接受水杨酸酯治疗的实验对象下丘（IC）中的GAD水平显著升高了63%（P<0.008）。这一情况发生在表现出耳鸣行为证据的实验对象身上。蝇蕈醇饱和分析表明，受体亲和力出现了与水杨酸酯相关的增加。[(3)H]蝇蕈醇饱和分析数据的线性回归显示，整个IC（-48%）以及IC的中央核（CIC，-58%）和IC的联合外侧及背侧皮质（E/DCIC，-46%）中的解离常数（K(d)）值显著降低（P<0.05）。GABA(A)结合位点的数量（B(max)）也显著减少（P<0.05）。这些变化仅在中枢听觉结构中观察到。这表明，长期接触水杨酸钠可能会改变GAD的表达和GABA(A)受体的结合特性，而这些变化可能代表了临床上以耳鸣形式出现的异常可塑性。
