Electrical stimulation of the ventral hippocampal commissure delays experimental epilepsy and is associated with altered microRNA expression
Electrical stimulation of the ventral hippocampal commissure delays experimental epilepsy and is associated with altered microRNA expression
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DOI：
10.1016/j.brs.2019.06.009
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发表时间：
2019-11-01
影响因子：
7.7
通讯作者：
Bauer, Sebastian
中科院分区：
文献类型：
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作者：
Costard, Lara S.;Neubert, Valentin;Bauer, Sebastian
背景资料：高达80%的内侧颞叶癫痫伴海马硬化（mTLE-HS）患者对药物治疗有抵抗力，通常需要手术切除。脑深部电刺激（DBS）已成为不符合切除性脑手术条件的患者的替代治疗方法。脑刺激也可能发挥疾病修饰的效果，和非编码microRNAs最近已被提出来塑造的基因表达景观在epileps.Objective：我们比较了DBS的4个不同的海马靶区域对癫痫发生和显性癫痫大鼠模型的mTLE-HS的效果。为了探索机制，我们分析了最有效的DBS范式对海马microRNAlevels.Methods的影响：MTLE-HS诱导大鼠的穿通通路（PP）的电刺激。这种模式导致4周内自发性癫痫发作。我们研究了4个靶点的DBS：PP，穹窿海马伞（FF）形成，齿状回（DG）和腹侧海马连合（VHC）。我们应用了高频（130 Hz）和低频（5 Hz或1 Hz）刺激。功能microRNAs在VHC-DBS后立即在海马和97天的记录期后，通过测序小RNA结合Argonaute-2，一个组成部分的miRNA silencingcomplex.Results：低频DBS的VHC显着延迟PPS模型中的第一次自发复发性癫痫发作的发生，从19至56天，相似的300%。没有其他刺激方案改变了潜伏期阶段。VHC-stimulation.Conclusion：我们得出结论，DBS的VHC延迟癫痫大鼠PPS模型中的5 microRNAs在癫痫发生过程中的上调被抑制，并与几个miRNA的差异调节。需要进一步的研究来确定VHC调节的miRNA是否在该DBS模型的抗癫痫作用中起因果作用。(C)2019爱思唯尔公司All rights reserved.
Background: Up to 80% of mesial temporal lobe epilepsy patients with hippocampal sclerosis (mTLE-HS) are resistant to pharmacological treatment, often necessitating surgical resection. Deep brain stimulation (DBS) has emerged as an alternative treatment for patients who do not qualify for resective brain surgery. Brain stimulation may also exert disease-modifying effects, and noncoding microRNAs have recently been proposed to shape the gene expression landscape in epilepsy.Objective: We compared the effect of DBS of 4 different hippocampal target regions on epileptogenesis and manifest epilepsy in a rat model of mTLE-HS. To explore mechanisms, we profiled the effect of the most effective DBS paradigm on hippocampal microRNA levels.Methods: MTLE-HS was induced by electrical stimulation of the perforant pathway (PP) in rats. This paradigm leads to spontaneous seizures within 4 weeks. We investigated DBS of 4 targets: PP, fimbria fornix (FF) formation, dentate gyrus (DG) and ventral hippocampal commissure (VHC). We applied both high- (130 Hz) and low-frequency (5 Hz or 1 Hz) stimulation. Functional microRNAs were identified in the hippocampus immediately after VHC-DBS and after a 97-day recording period by sequencing small RNAs bound to Argonaute-2, a component of the miRNA silencing complex.Results: Low frequency DBS of the VHC significantly delayed the occurrence of the first spontaneous recurrent seizure in the PPS model by similar to 300%, from 19 to 56 days. No other stimulation regime altered the latency phase. Upregulation of 5 microRNAs during epileptogenesis was suppressed by VHC-stimulation.Conclusion: We conclude that DBS of the VHC delays epilepsy in the PPS model in rats and is associated with differential regulation of several miRNAs. Additional studies are required to determine whether VHC-regulated miRNAs serve causal roles in the anti-epileptogenic effects of this DBS model. (C) 2019 Elsevier Inc. All rights reserved.