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毛果芸香碱在斑马鱼幼体中诱发癫痫发作及启动癫痫发生过程。

Induction of seizures and initiation of epileptogenesis by pilocarpine in zebrafish larvae.

作者信息

Gawel Kinga, Hulas-Stasiak Monika, Marszalek-Grabska Marta, Grenda Anna, Siekierska Aleksandra, Kosheva Nataliia, van der Ent Wietske, Esguerra Camila V, Krawczyk Pawel, Turski Waldemar A

机构信息

Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Lublin, Poland.

Department of Functional Anatomy and Cytobiology, Maria Curie-Sklodowska University, Lublin, Poland.

出版信息

Front Mol Neurosci. 2024 Aug 6;17:1418606. doi: 10.3389/fnmol.2024.1418606. eCollection 2024.

DOI:10.3389/fnmol.2024.1418606
PMID:39165716
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11333333/
Abstract

OBJECTIVE

Preclinical models of seizures and epilepsy in rodents contributed substantially to the discovery of currently available antiseizure medications. These were also broadly used for investigation of processes of epileptogenesis. Nevertheless, rodent models pose some limitations, thus, new models using alternative species are in high demand. The aim of this study was to describe a new model of seizures/epilepsy induced by the cholinomimetic agent, pilocarpine (PILO), in larval zebrafish.

METHODS

Local field potential (LFP) recordings were conducted to analyze electroencephalographic discharges and correlate it with larval behavior. Hematoxylin and eosin (H&E) staining, as well as TUNEL staining were performed to analyze morphology and apoptosis, respectively. Real-time quantitative polymerase chain reaction (qRT-PCR) was undertaken for gene expression analysis.

RESULTS

Acute exposure to PILO, in a concentration-dependent manner, induces electroencephalographic discharges in larval zebrafish, which behaviorally manifest as decreased locomotion and moving time, but enhanced movement velocity. The PILO-induced seizure-like activity is behaviorally distinct from this induced by the application of chemoconvulsant pentylenetetrazole (PTZ). Zebrafish larvae previously exposed to PILO (2 h), after a washing out period, exhibit spontaneous, unprovoked discharges and apoptotic changes in their brains.

SIGNIFICANCE

Here, we comprehensively investigated a new model of PILO-induced seizures/epilepsy in larval zebrafish. We propose that this model may be used to study epileptogenesis and for antiseizure drug screening purposes.

摘要

目的

啮齿动物的癫痫发作和癫痫临床前模型对当前可用抗癫痫药物的发现做出了重大贡献。这些模型也广泛用于癫痫发生过程的研究。然而，啮齿动物模型存在一些局限性，因此，对使用其他物种的新模型有很高的需求。本研究的目的是描述一种由拟胆碱剂毛果芸香碱（PILO）诱导的斑马鱼幼体癫痫发作/癫痫新模型。

方法

进行局部场电位（LFP）记录以分析脑电图放电，并将其与幼体行为相关联。分别进行苏木精和伊红（H&E）染色以及TUNEL染色以分析形态学和细胞凋亡。采用实时定量聚合酶链反应（qRT-PCR）进行基因表达分析。

结果

急性暴露于PILO以浓度依赖性方式诱导斑马鱼幼体的脑电图放电，其行为表现为运动和移动时间减少，但运动速度增加。PILO诱导的癫痫样活动在行为上与应用化学惊厥剂戊四氮（PTZ）诱导的活动不同。先前暴露于PILO（2小时）的斑马鱼幼体在洗脱期后表现出大脑中的自发性、无端放电和凋亡变化。

意义

在此，我们全面研究了一种由PILO诱导的斑马鱼幼体癫痫发作/癫痫新模型。我们提出该模型可用于研究癫痫发生和抗癫痫药物筛选。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb40/11333333/7796c7905337/fnmol-17-1418606-g008.jpg
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