Ramírez M, Gutiérrez R
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, del Instituto Politécnico Nacional, Apartado Postal 14-740, D.F. 07000, México, Mexico.
Brain Res. 2001 Nov 2;917(2):139-46. doi: 10.1016/s0006-8993(01)02794-9.
In the normal granule cells of the dentate gyrus glutamate, GABA and glutamic acid decarboxylase (GAD67) coexist. After kindled seizures, this enzyme is transiently overexpressed and simultaneous glutamatergic and GABAergic transmission in the mossy fiber projection occurs. Since this dual transmission is also seen after acutely-induced seizures, we decided to study the relationship between the expression of GAD67 and the induction of simultaneous glutamatergic and GABAergic transmission by kindled or acutely induced seizures. We also explored whether kindling of the dentate gyrus in vitro, that does not induce epileptiform activity, could induce the expression of GAD67. We confirm that kindling epilepsy induces the expression of GAD67 in the dentate gyrus. Despite the emergence of GABAergic transmission in the mossy fiber projection after a single seizure, GAD67 expression in the dentate gyrus appeared similar to controls, however, in the mossy fibers an enhanced immunostaining was evident. Interestingly, kindling the dentate gyrus in vitro induces a marked GAD67 staining in the granule cells. Our results show that after the activity-dependent emergence of simultaneous glutamatergic and GABAergic transmission from the mossy fibers, GAD67 is expressed in the mossy fibers and, upon long-lasting enduring stimulation periods, also in the dentate gyrus. Thus, this phenomenon does not depend on the presence of epileptic activity, but rather, on increased excitatory input onto the dentate gyrus. This can represent a protective mechanism that can sustain GABA synthesis in an activity-dependent manner.
在齿状回的正常颗粒细胞中，谷氨酸、γ-氨基丁酸（GABA）和谷氨酸脱羧酶（GAD67）共存。点燃性癫痫发作后，这种酶会短暂过度表达，并且在苔藓纤维投射中会同时发生谷氨酸能和GABA能传递。由于在急性诱发的癫痫发作后也能观察到这种双重传递，我们决定研究GAD67的表达与点燃性或急性诱发的癫痫发作所诱导的谷氨酸能和GABA能同时传递之间的关系。我们还探讨了在体外点燃齿状回（不会诱发癫痫样活动）是否能诱导GAD67的表达。我们证实点燃性癫痫会诱导齿状回中GAD67的表达。尽管单次癫痫发作后苔藓纤维投射中出现了GABA能传递，但齿状回中的GAD67表达与对照组相似，然而，在苔藓纤维中免疫染色增强是明显的。有趣的是，在体外点燃齿状回会在颗粒细胞中诱导明显的GAD67染色。我们的结果表明，在苔藓纤维中谷氨酸能和GABA能同时传递依赖活动出现后，GAD67在苔藓纤维中表达，并且在长期持续刺激后，也会在齿状回中表达。因此，这种现象不依赖于癫痫活动的存在，而是依赖于齿状回上兴奋性输入的增加。这可能代表一种保护机制，能够以依赖活动的方式维持GABA的合成。
