Murashima Y L, Kasamo K, Suzuki J
Department of Neurophysiology, Tokyo Institute of Psychiatry, Japan.
Epilepsy Res. 1998 Sep;32(1-2):254-65. doi: 10.1016/s0920-1211(98)00056-4.
We have investigated the potential antiepileptic action of superoxide dismutase (SOD) activities in the brain of the epileptic mutant EL mouse. EL mice which experienced frequent seizures (EL[s]) had abnormally low levels of SOD isoenzyme activity in the hippocampal area. Once epileptogenicity was established in these animals, activity of cyanide-sensitive Cu,Zn-SOD was maintained at significantly lower levels than in control mice. However, cyanide-insensitive Mn-SOD activity was not different from non-epileptic controls. In EL mice which had not experienced seizure provoking stimulations and exhibited no seizures (EL[ns]) there was moderately lower levels of SOD isoenzyme activities compared to controls. In spite of the low level of Cu,Zn-SOD activity in EL[s] mice, the Cu,Zn-SOD protein content was high in the hippocampus of these animals, suggesting that inactive Cu,Zn-SOD might be induced during development. After allopurinol (ALP) was given orally to EL[s] mice, Cu,Zn-SOD activities increased dramatically in the hippocampus and seizure activity was decreased. Even after 48 h, when antiepileptic action of ALP was lost, the SOD activity was maintained at the high level associated with initial ALP administration. EL[s] mice also showed DNA fragmentation in the hippocampal CA1 region and the parietal cortex, detected with in situ terminal transferase-mediated dUTP nick labeling with the aid of alkaliphosphatase or peroxidase. The degree of DNA fragmentation was less severe in EL[ns] mice. We propose that abnormalities in region specific Cu,Zn-SOD isoenzyme activity might produce free radicals, leading to DNA fragmentations and cell loss. This might contribute to hippocampal epileptogenesis in EL mice.
我们研究了超氧化物歧化酶（SOD）活性在癫痫突变体EL小鼠大脑中的潜在抗癫痫作用。经历频繁癫痫发作的EL小鼠（EL[s]）海马区的SOD同工酶活性异常低。一旦在这些动物中确立了癫痫源性，对氰化物敏感的铜锌超氧化物歧化酶（Cu,Zn-SOD）活性维持在明显低于对照小鼠的水平。然而，对氰化物不敏感的锰超氧化物歧化酶（Mn-SOD）活性与非癫痫对照无差异。在未经历诱发癫痫刺激且未出现癫痫发作的EL小鼠（EL[ns]）中，与对照相比，SOD同工酶活性略低。尽管EL[s]小鼠的铜锌超氧化物歧化酶活性水平较低，但这些动物海马中的铜锌超氧化物歧化酶蛋白含量较高，这表明无活性的铜锌超氧化物歧化酶可能在发育过程中被诱导产生。给EL[s]小鼠口服别嘌呤醇（ALP）后，海马中的铜锌超氧化物歧化酶活性显著增加，癫痫活动减少。即使在48小时后，当ALP的抗癫痫作用消失时，超氧化物歧化酶活性仍维持在与最初给予ALP时相关的高水平。EL[s]小鼠在海马CA1区和顶叶皮质也表现出DNA片段化，这是通过碱性磷酸酶或过氧化物酶辅助的原位末端转移酶介导的dUTP缺口标记检测到的。EL[ns]小鼠的DNA片段化程度较轻。我们提出，区域特异性铜锌超氧化物歧化酶同工酶活性异常可能产生自由基，导致DNA片段化和细胞丢失。这可能有助于EL小鼠海马癫痫的发生。
