Physiology and Pharmacology Department, Faculty of Medicine, Alborz University of Medical Sciences, Karaj, Alborz, Iran.
Department of Obstetrics and Gynecology, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
Behav Brain Res. 2021 Feb 5;399:112998. doi: 10.1016/j.bbr.2020.112998. Epub 2020 Nov 14.
Epilepsy is a chronic brain disease affecting millions of people worldwide. Anxiety-related disorders and cognitive deficits are common in patients with epilepsy. Previous studies have shown that maternal infection/immune activation renders children more vulnerable to neurological disorders later in life. Environmental enrichment has been suggested to improve seizures, anxiety, and cognitive impairment in animal models. The present study aimed to explore the effects of environmental enrichment on seizure scores, anxiety-like behavior, and cognitive deficits following maternal immune activation in offspring with epilepsy. Pregnant mice were treated with lipopolysaccharides-(LPS) or vehicle, and offspring were housed in normal or enriched environments during early adolescence to adulthood. To induce epilepsy, adult male and female offspring were treated with Pentylenetetrazol-(PTZ), and then anxiety-like behavior and cognitive functions were assessed. Tumor-necrosis-factor (TNF)-α and interleukin (IL) 10 were measured in the hippocampus of offspring. Maternal immune activation sex-dependently increased seizure scores in PTZ-treated offspring. Significant increases in anxiety-like behavior, cognitive impairment, and hippocampal TNF-α and IL-10 were also found following maternal immune activation in PTZ-treated offspring. However, there was no sex difference in these behavioral abnormalities in offspring. Environmental enrichment reversed the effects of maternal immune activation on behavioral and inflammatory parameters in PTZ-treated offspring. Overall, the present findings highlight the adverse effects of prenatal maternal immune activation on seizure susceptibility and psychiatric comorbidities in offspring. This study suggests that environmental enrichment may be used as a potential treatment approach for behavioral abnormalities following maternal immune activation in PTZ-treated offspring.
癫痫是一种影响全球数百万人的慢性脑部疾病。焦虑相关障碍和认知缺陷在癫痫患者中很常见。先前的研究表明，母体感染/免疫激活使儿童在以后的生活中更容易患神经障碍。环境丰富化已被证明可改善动物模型中的癫痫发作、焦虑和认知障碍。本研究旨在探讨环境丰富化对母体免疫激活后癫痫后代的癫痫发作评分、焦虑样行为和认知缺陷的影响。怀孕的老鼠接受脂多糖（LPS）或载体处理，在青春期到成年期，后代被安置在正常或丰富的环境中。为了诱导癫痫，成年雄性和雌性后代接受戊四氮（PTZ）处理，然后评估焦虑样行为和认知功能。在后代的海马体中测量肿瘤坏死因子（TNF）-α 和白细胞介素（IL）10。母体免疫激活在 PTZ 处理的后代中，性别依赖性地增加了癫痫发作评分。在 PTZ 处理的后代中，也发现了焦虑样行为、认知障碍以及海马体 TNF-α 和 IL-10 的显著增加，而母体免疫激活在 PTZ 处理的后代中并没有表现出这些行为异常的性别差异。环境丰富化逆转了母体免疫激活对 PTZ 处理后代行为和炎症参数的影响。总的来说，本研究结果强调了母体免疫激活对后代癫痫易感性和精神共病的不利影响。本研究表明，环境丰富化可能被用作 PTZ 处理后代母体免疫激活后行为异常的潜在治疗方法。
