内侧颞叶癫痫的新型大鼠婴儿模型揭示了发育中大脑分子生物学和癫痫发生的新见解。

IF 3 4区 医学 Q2 NEUROSCIENCES
Neural Plasticity Pub Date : 2024-07-25 eCollection Date: 2024-01-01 DOI:10.1155/2024/9946769
Carola Wormuth, Anna Papazoglou, Christina Henseler, Dan Ehninger, Karl Broich, Britta Haenisch, Jürgen Hescheler, Rüdiger Köhling, Marco Weiergräber
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引用次数: 0

摘要

虽然已经详细描述了几种成年大鼠内侧颞叶癫痫(mTLE)模型,但我们对婴儿大鼠内侧颞叶癫痫发病机制的了解还很有限。在此,我们介绍了一种新型的mTLE婴儿大鼠模型(InfRPil-mTLE),该模型是在产后第9、11和15天(pp)重复注射低剂量皮洛卡品(180毫克/千克。)该模型的存活率大于 80%,海马和皮层均表现出特征性的自发性复发性电图癫痫发作(SRES),并一直持续到成年。我们利用植入式视频脑电图放射遥测技术量化了一组复杂的癫痫发作参数,这些参数表明我们的InfRPil-mTLE模型诱导了慢性脑电图癫痫发作活动,这种活动在暗周期中占主导地位。我们使用 RT-qPCR 方法进一步分析了可能与癫痫发生相关的候选基因。一些候选基因,如低电压激活的Ca2+通道Cav3.2以及辅助亚基β1和β2,以前曾被报道在成人皮洛卡品mTLE模型的海马中上调,而在我们的InfRPil-mTLE模型的海马和皮层中,这些基因(连同Cav2.1、Cav2.3、M1和M3)被下调。从转化的角度来看,我们的模型可以作为儿童癫痫疾病的蓝图,并进一步促进未来抗癫痫药物的研究和开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A Novel Rat Infant Model of Medial Temporal Lobe Epilepsy Reveals New Insight into the Molecular Biology and Epileptogenesis in the Developing Brain.

Although several adult rat models of medial temporal lobe epilepsy (mTLE) have been described in detail, our knowledge of mTLE epileptogenesis in infant rats is limited. Here, we present a novel infant rat model of mTLE (InfRPil-mTLE) based on a repetitive, triphasic injection regimen consisting of low-dose pilocarpine administrations (180 mg/kg. i.p.) on days 9, 11, and 15 post partum (pp). The model had a survival rate of >80% and exhibited characteristic spontaneous recurrent electrographic seizures (SRES) in both the hippocampus and cortex that persisted into adulthood. Using implantable video-EEG radiotelemetry, we quantified a complex set of seizure parameters that demonstrated the induction of chronic electroencephalographic seizure activity in our InfRPil-mTLE model, which predominated during the dark cycle. We further analyzed selected candidate genes potentially relevant to epileptogenesis using a RT-qPCR approach. Several candidates, such as the low-voltage-activated Ca2+ channel Cav3.2 and the auxiliary subunits β 1 and β 2, which were previously reported to be upregulated in the hippocampus of the adult pilocarpine mTLE model, were found to be downregulated (together with Cav2.1, Cav2.3, M1, and M3) in the hippocampus and cortex of our InfRPil-mTLE model. From a translational point of view, our model could serve as a blueprint for childhood epileptic disorders and further contribute to antiepileptic drug research and development in the future.

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来源期刊
Neural Plasticity
Neural Plasticity NEUROSCIENCES-
CiteScore
6.80
自引率
0.00%
发文量
77
审稿时长
16 weeks
期刊介绍: Neural Plasticity is an international, interdisciplinary journal dedicated to the publication of articles related to all aspects of neural plasticity, with special emphasis on its functional significance as reflected in behavior and in psychopathology. Neural Plasticity publishes research and review articles from the entire range of relevant disciplines, including basic neuroscience, behavioral neuroscience, cognitive neuroscience, biological psychology, and biological psychiatry.
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