Korgan Austin C, Green Amanda D, Perrot Tara S, Esser Michael J
Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS, Canada.
Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS, Canada.
Behav Brain Res. 2014 Feb 1;259:106-18. doi: 10.1016/j.bbr.2013.10.037. Epub 2013 Nov 1.
Epilepsy is a relatively common and chronic neurological condition, affecting 1-2% of the population. However, understanding of the underlying pathophysiology remains incomplete. To identify potential factors in the early environment that may increase the risk for experiencing seizures, maternal stress and environmental enrichment (EE) were utilized. Pregnant Long-Evans rats were exposed to an ethologically relevant predator stress (PS) and maternal glucocorticoid (GC) response was assessed across the exposure period. At birth, litters were divided into standard care (SC) and EE groups until postnatal day 14 (PD14) when a model of febrile convulsions was used to determine seizure susceptibility of the various groups. Pup brains were then processed for immunohistochemical detection of FosB from several structures in the limbic system as a measure of neuronal activation. Maternal PS-induced GC levels were elevated early in the exposure period, and pup birth weights, in both sexes, were lower in litters from dams exposed to PS. Seizure scores at PD14 were highly individualized and litter dependent, suggesting a dam-dependent and variable effect of controlled pre- and postnatal environmental factors. Further, analysis of FosB-immunoreactive (-ir) patterns revealed an activity dependent distribution, reflecting individual seizure susceptibility. EE had a varying effect on FosB-ir that was dependent on region. In the hippocampus FosB-ir levels were greater in the EE groups while extra-hippocampal regions showed lower levels of FosB-ir. Our results support the concept that pre- and postnatal environmental influences affect fetal programming and neurodevelopment of processes that could underlie seizure susceptibility, but that the magnitude of these effects appears to be dam- or litter-dependent.
癫痫是一种相对常见的慢性神经系统疾病，影响着1%至2%的人口。然而，对其潜在病理生理学的理解仍不完整。为了确定早期环境中可能增加癫痫发作风险的潜在因素，研究采用了母体应激和环境富集（EE）的方法。将怀孕的Long-Evans大鼠暴露于符合行为学的捕食者应激（PS）中，并在整个暴露期间评估母体糖皮质激素（GC）反应。出生时，将幼崽分为标准护理（SC）组和EE组，直到出生后第14天（PD14），此时使用热性惊厥模型来确定各组的癫痫易感性。然后对幼崽大脑进行处理，以免疫组织化学方法检测边缘系统中几个结构的FosB，作为神经元激活的指标。母体PS诱导的GC水平在暴露期早期升高，暴露于PS的母鼠所产幼崽中，无论雌雄，出生体重均较低。PD14时的癫痫发作评分高度个体化且依赖于窝别，表明产前和产后环境因素的可控影响具有母鼠依赖性和变异性。此外，对FosB免疫反应性（-ir）模式的分析揭示了一种活动依赖性分布，反映了个体癫痫易感性。EE对FosB-ir的影响因区域而异。在海马体中，EE组的FosB-ir水平较高，而海马体外区域的FosB-ir水平较低。我们的结果支持这样的概念，即产前和产后环境影响会影响胎儿编程以及可能构成癫痫易感性基础的神经发育过程，但这些影响的程度似乎取决于母鼠或窝别。
