Transcriptome analysis of the hippocampal CA1 pyramidal cell region after kainic acid-induced status epilepticus in juvenile rats.
Transcriptome analysis of the hippocampal CA1 pyramidal cell region after kainic acid-induced status epilepticus in juvenile rats.
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DOI：
10.1371/journal.pone.0010733
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发表时间：
2010-05-20
期刊：
影响因子：
3.7
通讯作者：
Holopainen IE
中科院分区：
文献类型：
--
作者：
Laurén HB;Lopez-Picon FR;Brandt AM;Rios-Rojas CJ;Holopainen IE
在发育中的大脑癫痫发生的分子机制仍然知之甚少。基因阵列的方法可以揭示一些因素，通过允许识别大范围的基因改变癫痫发作。在这项研究中，我们使用微阵列分析揭示了21日龄大鼠在kainic酸（KA）诱导的癫痫持续状态（SE）后一周激光显微解剖海马CA1亚区基因表达谱，这些大鼠的发育大致与青少年相当。通过Chipster软件进行基因表达分析，ka处理大鼠的CA1亚区与对照大鼠相比，共有1592个不同表达的基因。KEGG数据库显示，鉴定的基因参与氧化磷酸化（26个基因改变）和长期增强（LTP， 18个基因改变）等途径。此外，参与Ca2+稳态、胶质细胞增生、炎症和gaba能传递的基因也发生了改变。为了验证微阵列结果，我们进一步检测了选定基因子集的蛋白表达，胶质纤维蛋白（GFAP），载脂蛋白E (apo E)，大麻素1型受体（CB1），浦肯野细胞蛋白4 （PEP-19）和白细胞介素8受体（CXCR1），免疫组织化学证实了转录组结果。我们的研究结果显示，SE没有导致CA1神经元的明显丢失，并且在癫痫发生早期，几个基因的表达模式的改变与之前的实验癫痫动物和颞叶癫痫（TLE）患者成年海马的基因表达研究相当。然而，一些变化似乎发生在SE后的幼鼠海马中。了解se诱导的基因表达改变及其相关途径可以为我们开发新的靶向性抗癫痫药物提供线索，这些药物可以干扰青少年年龄组疾病的进展。
Molecular mechanisms involved in epileptogenesis in the developing brain remain poorly understood. The gene array approach could reveal some of the factors involved by allowing the identification of a broad scale of genes altered by seizures. In this study we used microarray analysis to reveal the gene expression profile of the laser microdissected hippocampal CA1 subregion one week after kainic acid (KA)-induced status epilepticus (SE) in 21-day-old rats, which are developmentally roughly comparable to juvenile children. The gene expression analysis with the Chipster software generated a total of 1592 differently expressed genes in the CA1 subregion of KA-treated rats compared to control rats. The KEGG database revealed that the identified genes were involved in pathways such as oxidative phosporylation (26 genes changed), and long-term potentiation (LTP; 18 genes changed). Also genes involved in Ca2+ homeostasis, gliosis, inflammation, and GABAergic transmission were altered. To validate the microarray results we further examined the protein expression for a subset of selected genes, glial fibrillary protein (GFAP), apolipoprotein E (apo E), cannabinoid type 1 receptor (CB1), Purkinje cell protein 4 (PEP-19), and interleukin 8 receptor (CXCR1), with immunohistochemistry, which confirmed the transcriptome results. Our results showed that SE resulted in no obvious CA1 neuronal loss, and alterations in the expression pattern of several genes during the early epileptogenic phase were comparable to previous gene expression studies of the adult hippocampus of both experimental epileptic animals and patients with temporal lobe epilepsy (TLE). However, some changes seem to occur after SE specifically in the juvenile rat hippocampus. Insight of the SE-induced alterations in gene expression and their related pathways could give us hints for the development of new target-specific antiepileptic drugs that interfere with the progression of the disease in the juvenile age group.
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影响因子：
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