Seizing the moment: Zebrafish epilepsy models

Gaweł, Kinga; Langlois, Mélanie; Martins, Teresa G.; Ent, Wietske van der; Tiraboschi, Ettore; Jacmin, Maxime; Crawford, Alexander D.; Esguerra, Camila V.

doi:10.1016/j.neubiorev.2020.06.010

Cited by 71 publications

(80 citation statements)

References 234 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In conclusion, different zebrafish genetic models of epilepsy and to a lesser extent, SCZ, have emerged within the last 5 years (for comprehensive reviews see [106,107]). Although the zebrafish brain is less complex than the mammalian one, fish are very sensitive to neuroactive compounds and their behavioural responses are easily tracked in 48-well plates.…”

Section: Discussionmentioning

confidence: 99%

Zebrafish Larvae Carrying a Splice Variant Mutation in cacna1d: A New Model for Schizophrenia-Like Behaviours?

et al. 2020

Self Cite

View full text Add to dashboard Cite

Persons with certain single nucleotide polymorphisms (SNPs) in the CACNA1D gene (encoding voltage-gated calcium channel subunit alpha 1-D) have increased risk of developing neuropsychiatric disorders such as bipolar, schizophrenia and autism. The molecular consequences of SNPs on gene expression and protein function are not well understood. Thus, the use of animal models to determine genotype-phenotype correlations is critical to understanding disease pathogenesis. Here, we describe the behavioural changes in larval zebrafish carrying an essential splice site mutation (sa17298) in cacna1da. Heterozygous mutation resulted in 50% reduction of splice variants 201 and 202 (haploinsufficiency), while homozygosity increased transcript levels of variant 201 above wild type (WT; gain-of-function, GOF). Due to low homozygote viability, we focused primarily on performing the phenotypic analysis on heterozygotes. Indeed, cacna1dasa17298/WT larvae displayed hyperlocomotion—a behaviour characterised in zebrafish as a surrogate phenotype for epilepsy, anxiety or psychosis-like behaviour. Follow-up tests ruled out anxiety or seizures, however, as neither thigmotaxis defects nor epileptiform-like discharges in larval brains were observed. We therefore focused on testing for potential “psychosis-like” behaviour by assaying cacna1dasa17298/WT larval locomotor activity under constant light, during light-dark transition and in startle response to dark flashes. Furthermore, exposure of larvae to the antipsychotics, risperidone and haloperidol reversed cacna1da-induced hyperactivity to WT levels while valproate decreased but did not reverse hyperactivity. Together, these findings demonstrate that cacna1da haploinsufficiency induces behaviours in larval zebrafish analogous to those observed in rodent models of psychosis. Future studies on homozygous mutants will determine how cacna1d GOF alters behaviour in this context.

show abstract

Section: Discussionmentioning

confidence: 99%

Zebrafish Larvae Carrying a Splice Variant Mutation in cacna1d: A New Model for Schizophrenia-Like Behaviours?

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Numerous studies have suggested that zebrafish are a promising model for epileptic seizures and ASD screening [25][26][27]. The PTZ-induced zebrafish seizure model shares similar characteristics with mammals, including abnormal locomotor and electroencephalographic (EEG) activity and upregulation of c-fos expression, a biomarker of epileptic seizure [28][29][30].…”

Section: Discussionmentioning

confidence: 99%

Neurochemical Effects of 4-(2Chloro-4-Fluorobenzyl)-3-(2-Thienyl)-1,2,4-Oxadiazol-5(4H)-One in the Pentylenetetrazole (PTZ)-Induced Epileptic Seizure Zebrafish Model

Kim¹,

Kan²,

Hwang³

et al. 2021

IJMS

View full text Add to dashboard Cite

Epilepsy is one of the most common neurological disorders, and it is characterized by spontaneous seizures. In a previous study, we identified 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as a novel anti-epileptic agent in chemically- or genetically-induced epileptic zebrafish and mouse models. In this study, we investigated the anti-epileptic effects of GM-90432 through neurochemical profiling-based approach to understand the neuroprotective mechanism in a pentylenetetrazole (PTZ)-induced epileptic seizure zebrafish model. GM-90432 effectively improved PTZ-induced epileptic behaviors via upregulation of 5-hydroxytryptamine, 17-β-estradiol, dihydrotestosterone, progesterone, 5α -dihydroprogesterone, and allopregnanolone levels, and downregulation of normetanephrine, gamma-aminobutyric acid, and cortisol levels in brain tissue. GM-90432 also had a protective effect against PTZ-induced oxidative stress and zebrafish death, suggesting that it exhibits biphasic neuroprotective effects via scavenging of reactive oxygen species and anti-epileptic activities in a zebrafish model. In conclusion, our results suggest that neurochemical profiling study could be used to better understand of anti-epileptic mechanism of GM-90432, potentially leading to new drug discovery and development of anti-seizure agents.

show abstract

“…Additionally, using the PTZ larvael model, it was possible to track therapeutic genes and identify modular seizure genes, using genetic lines (45). Other studies using Zebrafish have evaluated different anticonvulsant drugs and vitamin K analogues (44).…”

Section: Epilepsymentioning

confidence: 99%

“…Neurological Disorders 5, 114, 129 P Produção 5,23,26,57,59,79,83,90,91,92,96,97,98,99,107,112 Pureza 5,7,44,45,46,48,49,50,51,52,60,62,66 R Radiologia 7,37,38,40,41,42 Reações a drogas 5,33,34 RNA 5,7,60,61,62,63,64,65,66,67,68,69,70,71,77,…”

mentioning

confidence: 99%

Alterações Genotóxicas, Citotóxicas E Mutagênicas: Um Conteúdo a Ser Ilustrado E Trabalhado No Ensino Médio

Brito¹,

Chagas²,

Messias³

et al. 2021

A Genética E a Construção De Novos Paradigmas Nas Ciências Da Vida

View full text Add to dashboard Cite

Direitos para esta edição cedidos à Atena Editora pelos autores. Todo o conteúdo deste livro está licenciado sob uma Licença de Atribuição Creative Commons. Atribuição-Não-Comercial-NãoDerivativos 4.0 Internacional (CC BY-NC-ND 4.0). O conteúdo dos artigos e seus dados em sua forma, correção e confiabilidade são de responsabilidade exclusiva dos autores, inclusive não representam necessariamente a posição oficial da Atena Editora. Permitido o download da obra e o compartilhamento desde que sejam atribuídos créditos aos autores, mas sem a possibilidade de alterá-la de nenhuma forma ou utilizá-la para fins comerciais. Todos os manuscritos foram previamente submetidos à avaliação cega pelos pares, membros do Conselho Editorial desta Editora, tendo sido aprovados para a publicação com base em critérios de neutralidade e imparcialidade acadêmica. A Atena Editora é comprometida em garantir a integridade editorial em todas as etapas do processo de publicação, evitando plágio, dados ou resultados fraudulentos e impedindo que interesses financeiros comprometam os padrões éticos da publicação. Situações suspeitas de má conduta científica serão investigadas sob o mais alto padrão de rigor acadêmico e ético.

show abstract

Seizing the moment: Zebrafish epilepsy models

Cited by 71 publications

References 234 publications

Zebrafish Larvae Carrying a Splice Variant Mutation in cacna1d: A New Model for Schizophrenia-Like Behaviours?

Zebrafish Larvae Carrying a Splice Variant Mutation in cacna1d: A New Model for Schizophrenia-Like Behaviours?

Neurochemical Effects of 4-(2Chloro-4-Fluorobenzyl)-3-(2-Thienyl)-1,2,4-Oxadiazol-5(4H)-One in the Pentylenetetrazole (PTZ)-Induced Epileptic Seizure Zebrafish Model

Alterações Genotóxicas, Citotóxicas E Mutagênicas: Um Conteúdo a Ser Ilustrado E Trabalhado No Ensino Médio

Contact Info

Product

Resources

About