Brandt Claudia, Bankstahl Marion, Töllner Kathrin, Klee Rebecca, Löscher Wolfgang
Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany.
Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany.
Epilepsy Behav. 2016 Aug;61:141-152. doi: 10.1016/j.yebeh.2016.05.020. Epub 2016 Jun 23.
Rat strains such as Sprague-Dawley (SD) or Wistar are widely used in epilepsy research, including popular models of temporal lobe epilepsy in which spontaneous recurrent seizures (SRS), hippocampal damage, and behavioral alterations develop after status epilepticus (SE). Such rats are randomly outbred, and outbred strains are known to be genetically heterogeneous populations with a high intrastrain variation. Intrastrain differences may be an important reason for discrepancies between studies from different laboratories, but the extent to which such differences affect the development of seizures, neurodegeneration, and psychopathology in post-SE models of epilepsy has received relatively little attention. In the present study, we induced SE by systemic administration of pilocarpine (following pretreatment with lithium) in SD rats from different breeders (Harlan, Charles River [CRL], Taconic) as well as different breeding locations of the same breeder (Harlan-Winkelmann [HW] in Germany vs. Harlan Laboratories [HL] in the Netherlands). Some experiments were also performed in Wistar rats. Pilocarpine was administered by a ramp-up dosing protocol that allows determining interindividual differences in susceptibility to the convulsant. Marked intrastrain differences in induction of SE and its long-term consequences were found. Sprague-Dawley rats from HW were significantly more sensitive to SE induction than all other SD substrains. The majority of SD rats from different vendors developed SRS after SE except SD rats from HL. The CRL-SD rats markedly differed in basal behavior and SE-induced behavioral alterations from other SD substrains. Susceptibility to pilocarpine was hardly affected by the estrous cycle. The marked intrastrain differences provide an interesting tool to study the impact of genetic and environmental factors on seizure susceptibility, epileptogenesis, and relationship between behavior and epilepsy and vice versa.
诸如斯普拉格-道利（SD）或威斯塔等大鼠品系广泛应用于癫痫研究，包括颞叶癫痫的常见模型，在这些模型中，癫痫持续状态（SE）后会出现自发反复癫痫发作（SRS）、海马损伤和行为改变。此类大鼠为随机远交系，已知远交系是基因异质性群体，品系内变异较高。品系内差异可能是不同实验室研究结果存在差异的重要原因，但在癫痫SE后模型中，此类差异对癫痫发作发展、神经退行性变和精神病理学的影响程度相对较少受到关注。在本研究中，我们通过对来自不同繁育商（哈兰、查尔斯河[CRL]、塔科尼克）以及同一繁育商不同繁育地点（德国的哈兰-温克尔曼[HW]与荷兰的哈兰实验室[HL]）的SD大鼠全身注射匹鲁卡品（锂预处理后）诱导SE。部分实验也在威斯塔大鼠中进行。匹鲁卡品通过逐步递增给药方案给药，该方案可确定个体对惊厥剂的易感性差异。我们发现SE诱导及其长期后果存在显著的品系内差异。来自HW的斯普拉格-道利大鼠对SE诱导的敏感性明显高于所有其他SD亚系。除来自HL的SD大鼠外，来自不同供应商的大多数SD大鼠在SE后出现了SRS。CRL-SD大鼠在基础行为和SE诱导的行为改变方面与其他SD亚系明显不同。发情周期对匹鲁卡品易感性几乎没有影响。显著的品系内差异为研究遗传和环境因素对癫痫易感性、癫痫发生以及行为与癫痫之间关系的影响提供了一个有趣的工具。
