Nehlig A, Vergnes M, Boyet S, Marescaux C
INSERM U 398, Université Louis Pasteur, Strasbourg, France.
Brain Res Dev Brain Res. 1998 Jun 15;108(1-2):69-75. doi: 10.1016/s0165-3806(98)00031-5.
In the present study, we measured basal local cerebral metabolic rates for glucose (LCMRglcs) in immature genetic absence epilepsy rats from Strasbourg (GAERS) at postnatal day 21 (P21), at which age no spike-and-wave discharges can be recorded. LCMRglcs in GAERS were compared to those in control non-epileptic (NE) rats of the same age selected from our breeding colony. LCMRglcs were measured in 60 structures by the quantitative [14C]2-deoxyglucose (2DG) autoradiographic technique. In P21 GAERS, LCMRglcs were similar to those of P21 NE rats in 46 areas. They increased over NE control levels in two groups of structures. First, metabolic increases were recorded in limbic structures such as entorhinal and piriform cortex, lateral septum as well as all hippocampal subfields and basolateral amygdala, although no spike-and-wave discharges can be recorded from those areas in adult GAERS. On the other hand, increases in LCMRglcs were also recorded in substantia nigra pars reticulata, superior colliculus and globus pallidus which are structures involved in the control of seizure activity. Finally, significant metabolic decreases in P21 GAERS were recorded in two posterior auditory regions, the inferior colliculus and the superior olive. In conclusion, our data show that the genetic mutation(s) underlying the cellular and molecular events responsible for the expression of spike-and-wave discharges in adult GAERS is(are) able to increase metabolic activity in limbic structures and in the nigral inhibitory system before the occurrence of absence seizures. Conversely, the full electrocortical maturation seems necessary for the expression of spike-and-wave discharges with the concurrent increase in LCMRglcs in adult GAERS.
在本研究中,我们测量了出生后第21天(P21)来自斯特拉斯堡的未成熟遗传性失神癫痫大鼠(GAERS)的基础局部脑葡萄糖代谢率(LCMRglcs),在这个年龄无法记录到棘波和慢波放电。将GAERS的LCMRglcs与从我们的繁殖群体中挑选出的同年龄对照非癫痫(NE)大鼠的LCMRglcs进行比较。通过定量[14C]2-脱氧葡萄糖(2DG)放射自显影技术在60个脑区测量LCMRglcs。在P21的GAERS中,46个脑区的LCMRglcs与P21的NE大鼠相似。在两组脑区中,它们高于NE对照水平。首先,在边缘结构如内嗅皮层、梨状皮层、外侧隔以及所有海马亚区和基底外侧杏仁核中记录到代谢增加,尽管在成年GAERS中这些区域无法记录到棘波和慢波放电。另一方面,在参与癫痫发作活动控制的黑质网状部、上丘和苍白球中也记录到LCMRglcs增加。最后,在P21的GAERS中,两个后听觉区域即下丘和上橄榄核记录到显著的代谢降低。总之,我们的数据表明,导致成年GAERS中棘波和慢波放电表达的细胞和分子事件背后的基因突变能够在失神发作出现之前增加边缘结构和黑质抑制系统中的代谢活动。相反,在成年GAERS中,完全的皮质电成熟似乎是棘波和慢波放电表达以及LCMRglcs同时增加所必需的。