Schwarzer C, Sperk G
Department of Pharmacology, University of Innsbruck, Austria.
Neuroscience. 1995 Dec;69(3):705-9. doi: 10.1016/0306-4522(95)00348-m.
Temporal lobe epilepsy is the most common form of epilepsy. Decreased GABA-ergic inhibition has been suggested as one cause of hyperexcitability. On the other hand, increased expression of glutamic acid decarboxylase, the rate-limiting enzyme of GABA synthesis, has been found in interneurons of the hippocampus in patients with temporal lobe epilepsy and in rats after kainic acid-induced limbic seizures, indicating increased GABA-ergic transmission. Here we report differential expression of two genes encoding different molecular forms of glutamic acid decarboxylase (GAD), GAD65 and GAD67, after kainic acid-induced seizures in the rat. There is a rapid but transient elevation of GAD67 mRNA levels in granule cells 6-24 h after kainic acid injection, followed by enhanced GAD immunoreactivity in the terminal field of mossy fibers. In interneurons in the hilus of the dentate gyrus, a sustained and progressing increase in the expression of both GAD65 and GAD67 messenger RNA occurs. These observations indicate that consitutively glutamatergic mossy fibers may be capable of synthetizing and utilizing the inhibitory transmitter GABA in sustained limbic seizures. Enhanced expression of glutamic acid decarboxylases within interneurons and in granule cells/mossy fibers suggest augmented GABA-ergic neurotransmission supporting selfprotective, anticonvulsive mechanisms in limbic epilepsy.
颞叶癫痫是最常见的癫痫类型。γ-氨基丁酸（GABA）能抑制作用减弱被认为是兴奋性过高的一个原因。另一方面，在颞叶癫痫患者的海马中间神经元以及海藻酸诱导边缘性癫痫发作后的大鼠中，已发现GABA合成的限速酶谷氨酸脱羧酶的表达增加，这表明GABA能传递增强。在此，我们报告了在大鼠海藻酸诱导癫痫发作后，编码谷氨酸脱羧酶（GAD）不同分子形式的两个基因GAD65和GAD67的差异表达。海藻酸注射后6 - 24小时，颗粒细胞中GAD67 mRNA水平迅速但短暂升高，随后苔藓纤维终末区域的GAD免疫反应性增强。在齿状回门区的中间神经元中，GAD65和GAD67信使RNA的表达持续且逐渐增加。这些观察结果表明，在持续性边缘性癫痫发作中，组成性谷氨酸能苔藓纤维可能能够合成并利用抑制性递质GABA。中间神经元以及颗粒细胞/苔藓纤维中谷氨酸脱羧酶表达的增强表明，GABA能神经传递增强，支持边缘性癫痫中的自我保护、抗惊厥机制。
