Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA; Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Exp Neurol. 2014 Jun;256:74-80. doi: 10.1016/j.expneurol.2014.03.014. Epub 2014 Mar 29.
Children with epilepsy show a high co-morbidity with psychiatric disorders and autism. One of the critical determinants of a child's behavioral outcome with autism and cognitive dysfunction is the age of onset of seizures. In order to examine whether seizures during postnatal days 7-11 result in learning and memory deficits and behavioral features of autism we administered the inhalant flurothyl to induce seizures in C57BL/6J mice. Mice received three seizures per day for five days starting on postnatal day 7. Parallel control groups consisted of similarly handled animals that were not exposed to flurothyl and naïve mice. Subjects were then processed through a battery of behavioral tests in adulthood: elevated-plus maze, nose-poke assay, marble burying, social partition, social chamber, fear conditioning, and Morris water maze. Mice with early-life seizures had learning and memory deficits in the training portion of the Morris water maze (p<0.05) and probe trial (p<0.01). Mice with seizures showed no differences in marble burying, the nose-poke assay, or elevated plus-maze testing compared to controls. However, they showed a significant difference in the social chamber and social partition tests. Mice with seizures during postnatal days 7-11 showed a significant decrease in social interaction in the social chamber test and had a significant impairment in social behavior in the social partition test. Together, these results indicate that early life seizures result in deficits in hippocampal-dependent memory tasks and produce long-term disruptions in social behavior.
患有癫痫的儿童与精神障碍和自闭症的共病率很高。自闭症和认知功能障碍儿童行为结果的关键决定因素之一是癫痫发作的年龄。为了研究出生后第 7-11 天的癫痫发作是否会导致学习和记忆缺陷以及自闭症的行为特征,我们给 C57BL/6J 小鼠施用吸入氟烷来诱发癫痫发作。从第 7 天开始,每天给小鼠 3 次癫痫发作,连续 5 天。平行对照组由同样处理但未暴露于氟烷的动物和未处理的小鼠组成。然后,对成年后的一系列行为测试进行处理:高架十字迷宫、鼻刺试验、大理石掩埋、社交分区、社交室、恐惧条件反射和莫里斯水迷宫。在生命早期发生癫痫发作的小鼠在莫里斯水迷宫的训练部分(p<0.05)和探测试验(p<0.01)中表现出学习和记忆缺陷。与对照组相比,癫痫发作的小鼠在大理石掩埋、鼻刺试验或高架十字迷宫测试中没有差异。然而,它们在社交室和社交分区测试中表现出显著差异。在出生后第 7-11 天发生癫痫发作的小鼠在社交室测试中的社交互动明显减少,在社交分区测试中的社交行为明显受损。总之,这些结果表明,生命早期的癫痫发作导致海马依赖性记忆任务的缺陷,并产生长期的社交行为障碍。