Department of Auditory Neuroscience, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Exp Gerontol. 2009 Mar;44(3):161-9. doi: 10.1016/j.exger.2008.09.012. Epub 2008 Oct 4.
Changes in the levels of gamma-aminobutyric acid (GABA) are known to occur in different parts of the brain during aging. In our study we attempted to define the effect that aging has on glutamate decarboxylase (GAD), the key enzyme in the synthesis of GABA, in the central parts of the auditory system. Age-related changes in GAD65 and GAD67 levels were investigated using immunohistochemistry and Western blotting in the inferior colliculus (IC), the auditory cortex (AC) and the visual cortex in Long-Evans rats. The results show that aging is associated with a decrease in the numbers of GAD65- and 67-immunoreactive neurons and the optical density of their somas in both the IC and AC. Western blot analysis revealed a pronounced age-related decline in the levels of GAD65 and 67 proteins in both the IC and AC. For comparison, in the visual cortex the decrease in both proteins was less pronounced than in the IC and AC. A similar pattern of age-related changes was found in Fischer 344 rats, a strain that manifests a rapid loss of hearing function with aging. The observed age-related decline in the levels of GAD65 and 67 may contribute significantly to the deterioration of hearing function that accompanies aging in mammals, including man.
已知γ-氨基丁酸（GABA）水平的变化会发生在大脑不同部位的衰老过程中。在我们的研究中，我们试图定义衰老对谷氨酸脱羧酶（GAD）的影响，GAD 是 GABA 合成的关键酶，在听觉系统的中枢部分。使用免疫组织化学和 Western blot 技术研究了老年长耳大鼠下丘（IC）、听觉皮层（AC）和视觉皮层中 GAD65 和 GAD67 水平的年龄相关性变化。结果表明，衰老与 IC 和 AC 中 GAD65 和 67-免疫反应性神经元数量以及其体部的光密度减少有关。Western blot 分析显示，IC 和 AC 中 GAD65 和 67 蛋白水平均明显随年龄下降。相比之下，在视觉皮层中，两种蛋白的减少程度均小于 IC 和 AC。在表现出听觉功能随衰老迅速丧失的 Fischer 344 大鼠中也发现了类似的与年龄相关的变化模式。GAD65 和 67 水平的观察到的与年龄相关的下降可能会显著导致包括人类在内的哺乳动物衰老过程中听力功能的恶化。
