University of Catanzaro, School of Medicine, Science of Health Dept., Catanzaro, Italy.
University of Catanzaro, School of Medicine, Science of Health Dept., Catanzaro, Italy.
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Aug 30;94:109652. doi: 10.1016/j.pnpbp.2019.109652. Epub 2019 May 13.
Neuropsychiatric comorbidities are common in patients with epilepsy, remaining still an urgent unmet clinical need. Therefore, the management of epileptic disorders should not only be restricted to the achievement of seizure-freedom but must also be able to counteract its related comorbidities. Experimental animal models of epilepsy represent a valid tool not only to study epilepsy but also its associated comorbidities. The WAG/Rij rat is a well-established genetically-based model of absence epilepsy with depressive-like comorbidity, in which learning and memory impairment was also recently reported. Aim of this study was to clarify whether this cognitive decline is secondary or not to absence seizures and/or depressive-like behavior. The behavioral performance of untreated and ethosuximide-treated (300 mg/kg/day; 17 days) WAG/Rij rats at 6 and 12 months of age were assessed in several tests: forced swimming test, objects recognition test, social recognition test, Morris water maze and passive avoidance. According to our results, it seems that cognitive impairment in this strain, similarly to depressive-like behavior, is secondary to the occurrence of absence seizures, which might be necessary for the expression of cognitive impairment. Furthermore, our results suggest an age-dependent impairment of cognitive performance in WAG/Rij rats, which could be linked to the age-dependent increase of spike wave discharges. Consistently, it is possible that absence seizures, depressive-like behavior and cognitive deficit may arise independently and separately in lifetime from the same underlying network disease, as previously suggested for the behavioral features associated with other epileptic syndromes.
神经精神共病在癫痫患者中很常见，仍然是一个亟待满足的临床需求。因此，癫痫疾病的管理不仅应局限于实现无癫痫发作，还必须能够对抗其相关共病。癫痫的实验动物模型不仅是研究癫痫的有效工具，也是研究其相关共病的有效工具。WAG/Rij 大鼠是一种成熟的遗传性癫痫伴抑郁样共病动物模型，最近也有报道称其存在学习记忆障碍。本研究旨在阐明这种认知障碍是否继发于癫痫发作和/或抑郁样行为。在 6 个月和 12 个月大时，对未经治疗和用乙琥胺（300mg/kg/天；17 天）治疗的 WAG/Rij 大鼠进行了多项测试，包括强迫游泳测试、物体识别测试、社交识别测试、Morris 水迷宫和被动回避测试，以评估其行为表现。根据我们的结果，WAG/Rij 大鼠的认知障碍似乎与抑郁样行为一样，是继发于癫痫发作的，而癫痫发作可能是认知障碍表达所必需的。此外，我们的结果表明 WAG/Rij 大鼠的认知表现存在年龄依赖性损伤，这可能与年龄依赖性棘波放电增加有关。一致地，正如先前对其他癫痫综合征相关行为特征的研究表明的那样，癫痫发作、抑郁样行为和认知缺陷可能在一生中独立于同一潜在网络疾病而分别出现。
