Singh Harsimran, Ramon Alfonsina, Finore Dana, Burnham Kaleigh, McRobert Scott, Lippman-Bell Jocelyn
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, PA, United States.
Department of Biology, Saint Joseph's University, Philadelphia, PA, United States.
Front Neurosci. 2022 Apr 22;16:869671. doi: 10.3389/fnins.2022.869671. eCollection 2022.
Early-life seizures (ELS) are often associated with the development of cognitive deficits. However, methods to predict and prevent these deficits are lacking. To increase the range of research models available to study cognitive consequences of ELS, we investigated whether seizures in larval zebrafish () lead to behavioral deficits later in life. We thus modified the existing pentylenetetrazole (PTZ)-induced seizure model in larval zebrafish, exposing zebrafish to PTZ daily from 5 to 7 days post-fertilization (dpf). We then compared later-life learning, social behavior (shoaling), and behavioral and chemical measures of anxiety in the PTZ-exposed zebrafish (PTZ group) to that of naïve clutchmates (untouched controls, UC) and to a second control group (handling control, HC) that experienced the same handling as the PTZ group, but without PTZ exposure. We observed that only the PTZ group displayed a significant deficit in a y-maze learning task, while only the HC group displayed a social deficit of decreased shoaling. HC fish also showed an increased frequency of behavioral freezing and elevated cortisol responses to netting, heightened stress responses not seen in the PTZ fish. Since mild stressors, such as the handling the HC fish experienced, can lead to learned, advantageous responses to stress later in life, we tested escape response in the HC fish using an acoustic startle stimulus. The HC group showed an enhanced startle response, swimming significantly farther than either the PTZ or UC group immediately after being startled. Taken together, these results indicate that seizures in larval zebrafish impair learning and the development of an adaptive, heightened stress response after early-life stress. These findings expand the behavioral characterization of the larval zebrafish seizure model, strengthening the power of this model for ELS research.
早期生活癫痫发作（ELS）通常与认知缺陷的发展有关。然而，目前缺乏预测和预防这些缺陷的方法。为了增加可用于研究ELS认知后果的研究模型的范围，我们研究了斑马鱼幼体的癫痫发作是否会导致其后期生活中的行为缺陷。因此，我们对现有的斑马鱼幼体戊四氮（PTZ）诱导的癫痫发作模型进行了修改，在受精后5至7天（dpf）每天让斑马鱼接触PTZ。然后，我们将接触PTZ的斑马鱼（PTZ组）与未接触过的同窝幼鱼（未接触对照组，UC）以及与PTZ组经历相同处理但未接触PTZ的第二个对照组（处理对照组，HC）在后期生活中的学习、社交行为（群居）以及行为和化学焦虑测量方面进行了比较。我们观察到，只有PTZ组在Y迷宫学习任务中表现出显著缺陷，而只有HC组表现出群居减少的社交缺陷。HC组的鱼还表现出行为静止频率增加以及对捞网的皮质醇反应升高，这是PTZ组鱼未出现的增强应激反应。由于轻度应激源，如HC组鱼所经历的处理，可导致后期生活中对应激产生习得性的、有利的反应，我们使用听觉惊吓刺激测试了HC组鱼的逃避反应。HC组表现出增强的惊吓反应，在受到惊吓后立即游动的距离明显比PTZ组或UC组更远。综上所述，这些结果表明，斑马鱼幼体的癫痫发作会损害学习以及早期生活应激后适应性增强应激反应的发展。这些发现扩展了斑马鱼幼体癫痫发作模型的行为特征，增强了该模型在ELS研究中的作用。
