Dufour Franck, Koning Estelle, Nehlig Astrid
INSERM U398, Université Louis Pasteur, Strasbourg, France.
Exp Neurol. 2003 Aug;182(2):346-52. doi: 10.1016/s0014-4886(03)00052-9.
The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are considered an isomorphic, predictive, and homologous model of human generalized absence epilepsy. It is characterized by the expression of spike-and-wave discharges in the thalamus and cortex. In this strain, basal regional rates of cerebral glucose utilization measured by the quantitative autoradiographic [(14)C]2-deoxyglucose technique display a widespread consistent increase compared to a selected strain of genetically nonepileptic rats (NE). In order to verify whether these high rates of glucose metabolism are paralleled by elevated activities of the enzymes of the glycolytic and tricarboxylic acid cycle pathways, we measured by histochemistry the regional activity of the two key enzymes of glucose metabolism, lactate dehydrogenase (LDH) for the anaerobic pathway and cytochrome oxidase (CO) for the aerobic pathway coupled to oxidative phosphorylation. CO and LDH activities were significantly higher in GAERS than in NE rats in 24 and 28 of the 30 brain regions studied, respectively. The differences in CO and LDH activity between both strains were widespread, affected all brain systems studied, and ranged from 12 to 63%. The data of the present study confirm the generalized increase in cerebral glucose metabolism in GAERS, occurring both at the glycolytic and at the oxidative step. However, they still do not allow us to understand why the ubiquitous mutation(s) generates spike-and-wave discharges only in the thalamocortical circuit.
来自斯特拉斯堡的遗传性失神癫痫大鼠(GAERS)被认为是人类全身性失神癫痫的同构、预测性和同源模型。其特征是丘脑和皮层出现棘波和慢波放电。在该品系中,通过定量放射自显影[(14)C]2-脱氧葡萄糖技术测量的脑葡萄糖利用基础区域速率与选定的遗传性非癫痫大鼠(NE)品系相比,呈现出广泛一致的增加。为了验证这些高葡萄糖代谢率是否与糖酵解和三羧酸循环途径的酶活性升高平行,我们通过组织化学测量了葡萄糖代谢的两种关键酶的区域活性,即厌氧途径的乳酸脱氢酶(LDH)和好氧途径与氧化磷酸化偶联的细胞色素氧化酶(CO)。在研究的30个脑区中的24个和28个区域,GAERS中的CO和LDH活性分别显著高于NE大鼠。两种品系之间CO和LDH活性的差异广泛,影响了所有研究的脑系统,范围从12%到63%。本研究的数据证实了GAERS中脑葡萄糖代谢的普遍增加,这在糖酵解和氧化步骤均有发生。然而,它们仍然无法让我们理解为什么这种普遍存在的突变仅在丘脑皮质回路中产生棘波和慢波放电。