Instituto de Medicina Molecular João Lobo Antunes, University of Lisbon, Lisbon, Portugal; Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
School of Psychology, Cardiff University, Cardiff, United Kingdom; Neuroscience Division, School of Bioscience, Cardiff University, Cardiff, United Kingdom.
Neurobiol Dis. 2023 Oct 1;186:106275. doi: 10.1016/j.nbd.2023.106275. Epub 2023 Aug 28.
Typical absence seizures (ASs) are brief periods of lack of consciousness, associated with 2.5-4 Hz spike-wave discharges (SWDs) in the EEG, which are highly prevalent in children and teenagers. The majority of probands in these young epileptic cohorts show neuropsychological comorbidities, including cognitive, memory and mood impairments, even after the seizures are pharmacologically controlled. Similar cognition and memory deficits have been reported in different, but not all, genetic animal models of ASs. However, since these impairments are subtle and highly task-specific their presence may be confounded by an anxiety-like phenotype and no study has tested anxiety and memory in the same animals. Moreover, the majority of studies used non-epileptic inbred animals as the only control strain and this may have contributed to a misinterpretation of these behavioural results. To overcome these issues, here we used a battery of behavioural tests to compare anxiety and memory in the same animals from the well-established inbred model of Genetic Absence Epilepsy Rats from Strasbourg (GAERS), their inbred strain of Non-Epileptic Control (NEC) strain (that lack ASs) and normal outbred Wistar rats. We found that GAERS do not exhibit increased anxiety-like behavior and neophobia compared to both NEC and Wistar rats. In contrast, GAERS show decreased spontaneous alternation, spatial working memory and cross-modal object recognition compared to both NEC and Wistar rats. Furthermore, GAERS preferentially used egocentric strategies to perform spatial memory tasks. In summary, these results provide solid evidence of memory deficits in GAERS rats that do not depend on an anxiety or neophobic phenotype. Moreover, the presence of differences between NEC and Wistar rats stresses the need of using both outbred and inbred control rats in behavioural studies involving genetic models of ASs.
典型失神发作（ASs）是短暂的意识丧失，脑电图（EEG）中伴有 2.5-4 Hz 棘慢波放电（SWDs），在儿童和青少年中非常普遍。这些年轻癫痫队列中的大多数患者都存在神经认知合并症，包括认知、记忆和情绪障碍，即使在癫痫发作得到药物控制后也是如此。在不同的但并非所有的 ASs 遗传动物模型中，都报道了类似的认知和记忆缺陷。然而，由于这些缺陷很细微且高度特定于任务，它们的存在可能会被类似焦虑的表型所混淆，而且没有研究在同一动物中同时测试焦虑和记忆。此外，大多数研究使用非癫痫的近交系动物作为唯一的对照品系，这可能导致对这些行为结果的错误解释。为了克服这些问题，我们在这里使用了一系列行为测试来比较在相同动物中，来自已建立的斯特拉斯堡遗传性失神癫痫大鼠（GAERS）的近交系、非癫痫对照（NEC）品系（不发生 ASs）和正常远交 Wistar 大鼠的焦虑和记忆。我们发现，GAERS 与 NEC 和 Wistar 大鼠相比，没有表现出增加的焦虑样行为和新异恐惧症。相比之下，GAERS 与 NEC 和 Wistar 大鼠相比，自发交替、空间工作记忆和跨模态物体识别能力下降。此外，GAERS 更倾向于使用自我中心策略来执行空间记忆任务。总之，这些结果为 GAERS 大鼠存在记忆缺陷提供了确凿的证据，而这些缺陷不依赖于焦虑或新异恐惧症表型。此外，NEC 和 Wistar 大鼠之间存在差异，这强调了在涉及 ASs 遗传模型的行为研究中，需要同时使用远交和近交对照大鼠。
