Department of Medical Neurosciences, Dalhousie University, Halifax, Nova Scotia, Canada.
Epilepsy Behav. 2013 Oct;29(1):19-27. doi: 10.1016/j.yebeh.2013.06.017. Epub 2013 Aug 7.
Epilepsy is a heterogeneous and chronic neurological condition of undefined etiology in the majority of cases. Similarly, the pathogenesis of the unprovoked seizures that lead to epilepsy is not known. We are interested in the factors that modify inherent seizure susceptibility, with a particular focus on those occurring during the prenatal and early postnatal periods. Female Sprague-Dawley rats were bred in-house or transported during pregnancy at one of two gestational days (G9 or G16). The effects of transport stress, maternal behavior, and offspring sex were then examined in terms of how they were related to provoked seizure susceptibility to kainic acid (KA) or a model of febrile convulsions (FCs) on postnatal day 14 (P14). We also examined the pattern of neuronal activation in the hippocampus and amygdala as indicated by the density of FosB protein immunoreactivity (FosB-ir). Results demonstrated only a small and inconsistent effect of transport alone, suggesting that the groups differed slightly prior to experimental manipulations. However, the influence of maternal behaviors such as licking and grooming (LG), arched back nursing (ABN), and dam-off time (DO) exerted a much stronger effect on the offspring. Dams designated as high LG gave birth to smaller litters, had pups that weighed less, had greater seizure susceptibility and severity, and had more FosB-ir neurons predominantly in the ventral hippocampus and the medial subnucleus of the amygdala (MeA). We also found a sex-dependent effect such that P14 males were smaller than their female littermates and had a greater seizure susceptibility and severity. Taken together, these results suggest an impact of prenatal and postnatal factors, as well as sex, on seizure susceptibility in young animals.
癫痫是一种异质性和慢性的神经疾病，在大多数情况下其病因不明。同样，导致癫痫的自发性癫痫发作的发病机制也不清楚。我们感兴趣的是改变内在癫痫易感性的因素，特别是在产前和产后早期发生的因素。雌性 Sprague-Dawley 大鼠在内部繁殖或在妊娠的两个孕日（G9 或 G16）之一进行运输。然后，根据它们与给予海人酸（KA）或发热性惊厥（FCs）模型的诱发癫痫易感性的关系，研究了运输应激、母性行为和后代性别等因素的影响，在产后第 14 天（P14）。我们还检查了海马体和杏仁核中的神经元激活模式，这是通过 FosB 蛋白免疫反应性（FosB-ir）的密度来表示的。结果仅显示单独运输的影响很小且不一致，这表明在进行实验操作之前，各组略有差异。然而，母性行为，如舔舐和梳理（LG）、拱形背部护理（ABN）和离乳时间（DO）的影响对后代的影响要大得多。被指定为高 LG 的母鼠所生的幼崽数量较少，体重较轻，癫痫易感性和严重程度较高，并且在腹侧海马体和杏仁核的内侧亚核（MeA）中具有更多的 FosB-ir 神经元。我们还发现了一种性别依赖性效应，即 P14 雄性比其雌性同窝仔小，并且癫痫易感性和严重程度更高。综上所述，这些结果表明产前和产后因素以及性别对幼小动物的癫痫易感性有影响。
