Cognitive and behavioral effects of brief seizures in mice

Cognitive and behavioral effects of brief seizures in mice
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DOI:
10.1016/j.yebeh.2019.07.015
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发表时间:
2019-09-01
影响因子:
2.6
通讯作者:
Ferraro, Thomas N.
Ferraro, Thomas N.
中科院分区:
医学3区
文献类型:
--
作者:
Batterman, Alexander, I;DeChiara, James;Ferraro, Thomas N.

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与癫痫相关的合并症大大降低了患者的生活质量。由于抗癫痫药物在改善认知和行为症状方面的成功有限,因此需要更好地了解癫痫相关认知和行为障碍的机制。解决这个问题的大多数先前研究都集中在慢性癫痫上,其中许多因素可以同时影响认知和行为。本研究的目的是使用小鼠开发一种测试范式,可以提供新的见解,了解急性癫痫发作的短期生物学变化如何影响认知和行为。在实验1中,幼稚的C57 BL/6 J小鼠进行了三个简短的,全身性电惊厥发作(ECS)或三个假治疗等间隔的过程中的30分钟。在接下来的2小时,小鼠进行了测试,在一个新的对象识别范例。后续研究检查运动活动之前和之后立即(实验2),之后立即(实验3),45分钟后(实验4)一组三个ECS或假治疗。然而,结果表明,有没有在识别记忆收购ECS和假治疗的小鼠之间的统计学上的显着差异,焦虑样行为的措施增加,减少新的物体的兴趣在ECS治疗的小鼠相比,在假。有趣的是,ECS也产生了延迟抑制作用的运动,减少开放领域的活动45分钟后处理相比,假手术。我们的结论是,短暂的癫痫发作的小灰尘可以有急性的,行为相关的影响,在小鼠,并应更加重视发生在慢性癫痫建立之前的事件,以更好地了解癫痫相关的认知和行为障碍。未来的研究将受益于使用上述定义的范例来研究单个癫痫发作对小鼠认知和行为的影响。(C)2019爱思唯尔公司All rights reserved.
Comorbidities associated with epilepsy greatly reduce patient's quality of life. Since antiepilepsy drugs show limited success in ameliorating cognitive and behavioral symptoms, there is a need to better understand the mechanisms underlying epilepsy-related cognitive and behavioral impairments. Most prior research addressing this problem has focused on chronic epilepsy, wherein many factors can simultaneously impact cognition and behavior. The purpose of the present study was to develop a testing paradigm using mice that can provide new insight into how short-term biological changes underlying acute seizures impact cognition and behavior. In Experiment 1, naive C57BL/6J mice were subjected to either three brief, generalized electroconvulsive seizure (ECS) or three sham treatments equally spaced over the course of 30 min. Over the next 2 h, mice were tested in a novel object recognition paradigm. Follow-up studies examined locomotor activity immediately before and after (Experiment 2), immediately after (Experiment 3), and 45 min after (Experiment 4) a set of three ECS or sham treatments. Whereas results demonstrated that there was no statistically significant difference in recognition memory acquisition between ECS and sham-treated mice, measures of anxiety-like behavior were increased and novel object interest was decreased in ECS-treated mice compared with that in sham. Interestingly, ECS also produced a delayed inhibitory effect on locomotion, decreasing open-field activity 45-min posttreatment compared to sham. We conclude that a small duster of brief seizures can have acute, behaviorally relevant effects in mice, and that greater emphasis should be placed on events that take place before chronic epilepsy is established in order to better understand epilepsy-related cognitive and behavioral impairments. Future research would benefit from using the paradigms defined above to study the effects of individual seizures on mouse cognition and behavior. (C) 2019 Elsevier Inc. All rights reserved.