Behavioral and cognitive alterations, spontaneous seizures, and neuropathology developing after a pilocarpine-induced status epilepticus in C57BL/6 mice
Behavioral and cognitive alterations, spontaneous seizures, and neuropathology developing after a pilocarpine-induced status epilepticus in C57BL/6 mice
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DOI：
10.1016/j.expneurol.2009.05.035
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发表时间：
2009-09-01
影响因子：
5.3
通讯作者：
Loescher, Wolfgang
中科院分区：
文献类型：
--
作者：
Mueller, Christine J.;Groeticke, Ina;Loescher, Wolfgang
许多癫痫患者患有精神共病，包括抑郁、焦虑、精神障碍、认知和人格改变，但癫痫与精神病理学之间关联的潜在机制尚不完全清楚。癫痫动物模型，例如获得性颞叶癫痫 (TLE) 的毛果芸香碱模型，可用于研究癫痫与行为功能障碍之间的关系。在本研究中，我们检查了 C57BL/6 (136) 近交系小鼠（通常用作转基因小鼠的背景品系）中毛果芸香碱诱导的癫痫持续状态后的行为和认知改变、自发性癫痫发作和神经病理学发展。在这项研究中，我们使用了与之前 NMRI 小鼠研究相同的毛果芸香碱递增剂量方案和行为测试电池，从而可以在这两种小鼠品系之间进行直接比较。所有在 SE 中幸存的 B6 小鼠均出现癫痫并伴有自发性复发性癫痫发作。癫痫B6小鼠在旷场和明暗箱中表现出与焦虑相关的行为显着增加，在旷场、高架十字迷宫、洞板和新物体探索测试中的运动活动增加，在强迫游泳和悬尾测试中不动性降低。此外，莫里斯水迷宫中的空间学习和记忆严重受损，尽管海马损伤比之前在 NMRI 小鼠中确定的要轻得多。毛果芸香碱不诱发 SE 但仅单次癫痫发作的 B6 小鼠没有表现出任何可检测到的神经变性，但在所用测试电池的多项测试中行为与假对照组不同。我们的数据表明，B6 小鼠的毛果芸香碱 TLE 模型非常适合研究癫痫发作、脑损伤和精神病理学之间关联的神经生物学机制。 (C) 2009 Elsevier Inc. 保留所有权利。
Many patients with epilepsy suffer from psychiatric comorbidities including depression, anxiety, psychotic disorders, cognitive, and personality changes, but the mechanisms underlying the association between epilepsy and psychopathology are only incompletely understood. Animal models of epilepsy, such as the pilocarpine model of acquired temporal lobe epilepsy (TLE), are useful to study the relationship between epilepsy and behavioral dysfunctions. In the present study, we examined behavioral and cognitive alterations, spontaneous seizures, and neuropathology developing after a pilocarpine-induced status epilepticus in the C57BL/6 (136) inbred strain of mice, which is commonly used as background strain for genetically modified mice. For this study, we used the same pilocarpine ramping-up dosing protocol and behavioral test battery than in a previous study in NMRI mice, thus allowing direct comparison between these two mouse strains. All B6 mice that survived SE developed epilepsy with spontaneous recurrent seizures. Epileptic B6 mice exhibited significant increases of anxiety-related behavior in the open field and light-dark box, increased locomotor activity in the open field, elevated plus maze, hole board, and novel object exploration tests, and decreased immobility in the forced swimming and tail suspension tests. Furthermore, spatial learning and memory were severely impaired in the Morris water maze, although hippocampal damage was much less severe than previously determined in NMRI mice. B6 mice in which pilocarpine did not induce SE but only single seizures did not exhibit any detectable neurodegeneration, but differed behaviorally from sham controls in several tests of the test battery used. Our data indicate that the pilocarpine model of TLE in B6 mice is ideally suited to study the neurobiological mechanisms underlying the association between seizures, brain damage and psychopathology. (C) 2009 Elsevier Inc. All rights reserved.