Expression Profiling after Prolonged Experimental Febrile Seizures in Mice Suggests Structural Remodeling in the Hippocampus.
Expression Profiling after Prolonged Experimental Febrile Seizures in Mice Suggests Structural Remodeling in the Hippocampus.
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DOI：
10.1371/journal.pone.0145247
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
de Graan PN
中科院分区：
文献类型：
--
作者：
Jongbloets BC;van Gassen KL;Kan AA;Olde Engberink AH;de Wit M;Wolterink-Donselaar IG;Groot Koerkamp MJ;van Nieuwenhuizen O;Holstege FC;de Graan PN
热性惊厥是5岁以下儿童中最常见的惊厥类型（占西欧儿童的2-4%）。复杂的热性癫痫发作与发展为颞叶癫痫的风险增加有关。为了研究实验性热性惊厥（eFS）的短期和长期影响，我们在出生后第10天通过高温暴露（HT）诱导高热惊厥易感C57BL/6J小鼠的eFS，并将其与正常暴露（NT）小鼠进行比较。我们在电刺激后14天检测到海马结构重组。为了确定携带这种结构重组的候选分子，我们研究了eFS后1小时至56天mRNA表达谱的时间变化。我们鉴定了931个调控基因，并在eFS后3天和14天使用原位杂交和组织学分析了几个候选基因。这是第一个报道小鼠eFS后全基因组转录组分析的研究。我们确定了多个过程的时间调节，如应激，免疫和炎症反应，胶质细胞激活，谷氨酸-谷氨酰胺循环和髓鞘形成。识别电磁场后的短期和长期变化对阐明癫痫发生的机制很重要。
Febrile seizures are the most prevalent type of seizures among children up to 5 years of age (2–4% of Western-European children). Complex febrile seizures are associated with an increased risk to develop temporal lobe epilepsy. To investigate short- and long-term effects of experimental febrile seizures (eFS), we induced eFS in highly febrile convulsion-susceptible C57BL/6J mice at post-natal day 10 by exposure to hyperthermia (HT) and compared them to normotherm-exposed (NT) mice. We detected structural re-organization in the hippocampus 14 days after eFS. To identify molecular candidates, which entrain this structural re-organization, we investigated temporal changes in mRNA expression profiles eFS 1 hour to 56 days after eFS. We identified 931 regulated genes and profiled several candidates using in situ hybridization and histology at 3 and 14 days after eFS. This is the first study to report genome-wide transcriptome analysis after eFS in mice. We identify temporal regulation of multiple processes, such as stress-, immune- and inflammatory responses, glia activation, glutamate-glutamine cycle and myelination. Identification of the short- and long-term changes after eFS is important to elucidate the mechanisms contributing to epileptogenesis.