Transcriptome profiling of hippocampal CA1 after early-life seizure-induced preconditioning may elucidate new genetic therapies for epilepsy.
Transcriptome profiling of hippocampal CA1 after early-life seizure-induced preconditioning may elucidate new genetic therapies for epilepsy.
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早期癫痫发作引起的预处理后，海马CA1的转录组分析可能阐明新的基因疗法癫痫。
DOI：
10.1111/ejn.12168
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发表时间：
2013-07
期刊：
影响因子：
--
通讯作者：
Spray DC
中科院分区：
文献类型：
--
作者：
Friedman LK;Mancuso J;Patel A;Kudur V;Leheste JR;Iacobas S;Botta J;Iacobas DA;Spray DC
在幼龄动物（P20）中单次注射红藻氨酸（1 × KA）诱导的CA 1亚区损伤在P6和P9有两次持续新生儿癫痫发作的动物中减弱。为了确定参与早期生活条件性癫痫发作产生的空间保护作用的候选基因，我们分析并比较了对照组、1 × KA处理组和3 × KA处理组动物的CA 1亚区转录组。3 × KA后表达上调的基因（9.6%）多于1 × KA后表达上调的基因（7.1%）。在1 × KA后，支持氧化应激、生长、发育、炎症和神经传递的基因上调（例如Cacng 1、Nadsyn 1、Kcng 1、Aven、S100 a4、GFAP、Vim、Hrsp 12和Grik 1）。3 × KA后，保护性基因差异过表达[例如Cat、Gpx 7、Gad 1、Hspa 12 A、Foxn 1、腺苷A1受体、Ca 2+适配器和稳态蛋白、Cacnb 4、Atp 2b 2、抗凋亡Bcl-2基因成员、细胞内运输蛋白、Grasp和细胞因子信号转导抑制因子（Socs 3）]。在成人组织中未观察到的独特抗炎性白细胞介素（IL）[例如IL-6转导子、IL-23和IL-33或其受体（IL-F2）]也过表达。通过实时聚合酶链反应（QPCR）和免疫组织化学验证了几种转录本。QPCR显示，casp 6在1 × KA后增加，但在3 × KA后减少;促炎基因Cox 1在1 × KA后上调或不变，但在3 × KA后减少约70%。1 × KA后增强的GFAP免疫染色在3 × KA后的CA 1亚区选择性减弱。观察到的差异转录反应可能通过减少谷氨酸受体介导的海马Ca 2+渗透性并重新定向炎症和细胞凋亡途径，有助于早期癫痫发作诱导的预处理和神经保护。这些变化可能导致新的癫痫基因疗法。
Injury of the CA1 subregion induced by a single injection of kainic acid (1 × KA) in juvenile animals (P20) is attenuated in animals with two prior sustained neonatal seizures on P6 and P9. To identify gene candidates involved in the spatially protective effects produced by early-life conditioning seizures we profiled and compared the transcriptomes of CA1 subregions from control, 1 × KA- and 3 × KA-treated animals. More genes were regulated following 3 × KA (9.6%) than after 1 × KA (7.1%). Following 1 × KA, genes supporting oxidative stress, growth, development, inflammation and neurotransmission were upregulated (e.g. Cacng1, Nadsyn1, Kcng1, Aven, S100a4, GFAP, Vim, Hrsp12 and Grik1). After 3 × KA, protective genes were differentially over-expressed [e.g. Cat, Gpx7, Gad1, Hspa12A, Foxn1, adenosine A1 receptor, Ca2+ adaptor and homeostasis proteins, Cacnb4, Atp2b2, anti-apoptotic Bcl-2 gene members, intracellular trafficking protein, Grasp and suppressor of cytokine signaling (Socs3)]. Distinct anti-inflammatory interleukins (ILs) not observed in adult tissues [e.g. IL-6 transducer, IL-23 and IL-33 or their receptors (IL-F2)] were also over-expressed. Several transcripts were validated by real-time polymerase chain reaction (QPCR) and immunohistochemistry. QPCR showed that casp 6 was increased after 1 × KA but reduced after 3 × KA; the pro-inflammatory gene Cox1 was either upregulated or unchanged after 1 × KA but reduced by ~70% after 3 × KA. Enhanced GFAP immunostaining following 1 × KA was selectively attenuated in the CA1 subregion after 3 × KA. The observed differential transcriptional responses may contribute to early-life seizure-induced pre-conditioning and neuroprotection by reducing glutamate receptor-mediated Ca2+ permeability of the hippocampus and redirecting inflammatory and apoptotic pathways. These changes could lead to new genetic therapies for epilepsy.
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DOI：
10.4269/ajtmh.2010.09-0399
发表时间：
2010-05-01
影响因子：
3.3
作者：
Adesse, Daniel;Iacobas, Dumitru A.;Spray, David C.
通讯作者：
Spray, David C.
影响因子：
6.1
作者：
Borges, Karin;Shaw, Renee;Dingledine, Raymond
通讯作者：
Dingledine, Raymond
DOI：
10.1016/j.ijdevneu.2009.11.002
发表时间：
2010-04-01
影响因子：
1.8
作者：
Friedman, Linda K.;Segal, Menahem
通讯作者：
Segal, Menahem
大鼠海马的定量转录神经解剖学：三个主要细胞层之间的广泛，途径特异性异质性的证据。
影响因子：
3.5
作者：
Greene, James G.;Borges, Karin;Dingledine, Raymond
通讯作者：
Dingledine, Raymond
影响因子：
6.1
作者：
Fan, Lir-Wan;Tien, Lu-Tai;Lin, Rick C. S.;Simpson, Kimberly L.;Rhodes, Philip G.;Cai, Zhengwei
通讯作者：
Cai, Zhengwei