miRNA Expression Profile after Status Epilepticus and Hippocampal Neuroprotection by Targeting miR-132
miRNA Expression Profile after Status Epilepticus and Hippocampal Neuroprotection by Targeting miR-132
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DOI：
10.1016/j.ajpath.2011.07.036
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发表时间：
2011-11-01
影响因子：
6
通讯作者：
Henshall, David C.
中科院分区：
文献类型：
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作者：
Jimenez-Mateos, Eva M.;Bray, Isabella;Henshall, David C.
当大脑受到短暂的非伤害性刺激后，大脑会变得宽容，从而减少对大脑的伤害。当短暂的癫痫发作先于长时间的癫痫发作（癫痫持续状态）时，癫痫耐受性就会发展。microRNA（miRNAs）是一类小的非编码RNA，在基因表达中起转录后调节作用。我们研究了预先癫痫预处理如何影响小鼠杏仁核内红藻氨酸诱发癫痫持续状态的miRNA反应。在局灶性发作癫痫持续状态后24小时，从先前接受过癫痫发作预处理（耐受）或未接受预处理（损伤）的动物中提取同侧CA 3子区的miRNA，并使用TagMan低密度阵列测量成熟miRNA水平。与对照组相比，单独癫痫持续状态后，21种miRNAs的表达增加，12种miRNAs的表达降低。miR-132水平的增加与Argonaute-2结合的增加相匹配，Argonaute-2是RNA诱导沉默复合物的一种成分。在耐受动物中，>40%的损伤组检测到的miRNA的表达反应不同，相对于对照组没有变化或下调，这包括miR-132。体内显微注射针对miR-132的锁核酸修饰的寡核苷酸（cumulomirs）耗尽海马miR-132水平并减少海马诱导的神经元死亡。因此，我们的数据有力地表明，miRNA是脑缺血诱导的神经元死亡的重要调节因子。(Am J Pathol 2011，179：2519-2532; DOI：10.1016/j.ajpath.2011.07.036）
When an otherwise harmful insult to the brain is preceded by a brief, noninjurious stimulus, the brain becomes tolerant, and the resulting damage is reduced. Epileptic tolerance develops when brief seizures precede an episode of prolonged seizures (status epilepticus). MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators of gene expression. We investigated how prior seizure preconditioning affects the miRNA response to status epilepticus evoked by intra-amygdalar kainic acid in mice. The miRNA was extracted from the ipsilateral CA3 subfield 24 hours after focal-onset status epilepticus in animals that had previously received either seizure preconditioning (tolerance) or no preconditioning (injury), and mature miRNA levels were measured using TagMan low-density arrays. Expression of 21 miRNAs was increased, relative to control, after status epilepticus alone, and expression of 12 miRNAs was decreased. Increased miR-132 levels were matched with increased binding to Argonaute-2, a constituent of the RNA-induced silencing complex. In tolerant animals, expression responses of >40% of the injury-group-detected miRNAs differed, being either unchanged relative to control or down-regulated, and this included miR-132. In vivo microinjection of locked nucleic acid-modified oligonucleotides (antagomirs) against miR-132 depleted hippocampal miR-132 levels and reduced seizure-induced neuronal death. Thus, our data strongly suggest that miRNAs are important regulators of seizure-induced neuronal death. (Am J Pathol 2011, 179:2519-2532; DOI: 10.1016/j.ajpath.2011.07.036)