Epileptic seizures induced by N-acetyl-L-aspartate in rats:: in vivo and in vitro studies
Epileptic seizures induced by N-acetyl-L-aspartate in rats:: in vivo and in vitro studies
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DOI：
10.1016/s0006-8993(00)02028-x
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发表时间：
2000-04-07
期刊：
影响因子：
2.9
通讯作者：
Sasa, M
中科院分区：
文献类型：
--
作者：
Akimitsu, T;Kurisu, K;Sasa, M
震颤大鼠 (tm/tm) 是自发性癫痫大鼠 (SER: zi/zi, tm/tm) 的亲本品系，在 10 周龄后，在发生惊厥性癫痫发作之前，在皮质和海马脑电图 (EEG) 上表现出以 5-7 Hz 棘波状复合体为特征的失神样癫痫发作。最近，该动物模型已被证明在天冬氨酸酰化酶水解 N-乙酰-L 天冬氨酸 (NAA) 所在的关键区域内显示出基因组微缺失，此外还显示出在大脑中积累 NAA 的能力。因此，本研究旨在确定 NAA 在诱发癫痫发作中的作用。当将NAA（4μmol）脑室内（i.c.v.）应用于正常Wistar大鼠时，在皮质和海马脑电图上观察到4-10 Hz多尖峰和/或尖峰波状复合物，随后出现失神样癫痫发作，然后在持续1-5 Hz蜡状高压后放电之前观察到。在较高剂量（8 μmol）下，NAA 会诱发惊厥性癫痫发作。脑电图上也观察到了具有多尖峰和/或尖波状复合体的失神样癫痫发作。 NAA 在不伴有癫痫发作的早发性震颤大鼠中的作用。正常大鼠中 NAA 诱导的癫痫发作可被静脉注射拮抗。谷氨酸二乙酯，一种非选择性谷氨酸受体拮抗剂。此外，在浴液中加入 NAA 后，会迅速诱导正常大鼠脑切片的海马 CA3 神经元重复放电，同时产生持久的去极化。这些发现表明，NAA 可能通过谷氨酸受体参与诱导失神样癫痫发作和/或惊厥。 (C) 2000 Elsevier Science B.V. 保留所有权利。
Tremor rat (tm/tm), the parent strain of spontaneously epileptic rat (SER: zi/zi, tm/tm), exhibits absence-like seizures characterized by 5-7 Hz spike-wave-like complexes on cortical and hippocampal electroencephalograms (EEG) after 10 weeks of age, prior to development of convulsive seizures. Recently, this animal model has been demonstrated to display a genomic microdeletion within the critical region of an, where aspartoacylase hydrolyzing N-acetyl-L aspartate (NAA) is located, besides showing the ability to accumulate NAA in the brain. Therefore, the present study was performed to determine the involvement of NAA in the induction of epileptic seizures. When NAA (4 mu mol) was applied intracerebroventricularly (i.c.v.) to normal Wistar rats, 4-10 Hz polyspikes and/or spike-wave-like complexes followed by absence-like seizure before persistent 1-5 Hz waxing high-voltage after-discharges were observed on cortical and hippocampal EEG. At a higher dose (8 mu mol), NAA induced convulsive seizures. The absence-like seizures with polyspikes and/or spike-wave-like complexes on the EEG were also observed with i.c.v. NAA in premature tremor rats without seizures. The NAA-induced seizures in normal rats were antagonized by i.c.v. glutamic acid diethyl ester, a non-selective glutamate receptor antagonist. In addition, NAA applied to the bath rapidly induced a :long-lasting depolarization concomitantly with repetitive firings in hippocampal CA3 neurons of normal rat brain slice preparations. These findings suggest that NAA is involved in the induction of absence-like seizures and/or convulsion, probably via glutamate receptors. (C) 2000 Elsevier Science B.V. All rights reserved.