Zebrafish models of autism spectrum disorder

Meshalkina, Darya A.; Kizlyk, Marina N.; Kysil, Elana V.; Collier, Adam D.; Echevarria, David J.; Abreu, Murilo S. de; Barcellos, Leonardo José Gil; Song, Cai; Warnick, Jason E.; Kyzar, Evan J.; Kalueff, Allan V.

doi:10.1016/j.expneurol.2017.02.004

Cited by 116 publications

(97 citation statements)

References 124 publications

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“…Specifically, we will focus on early phenotypes (morphological and behavioral), rather than adult behaviors, which have been addressed in detail in other reviews (Meshalkina et al, 2018; Shams et al, 2018). We will highlight insights into basic mechanisms of risk gene function and potential drug candidates identified in zebrafish models, as well as the limitations of studies to date.…”

Section: Introductionmentioning

confidence: 99%

Zebrafish Models of Neurodevelopmental Disorders: Past, Present, and Future

Sakai

Ijaz

Hoffman

2018

Front. Mol. Neurosci.

127

123

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Zebrafish are increasingly being utilized as a model system to investigate the function of the growing list of risk genes associated with neurodevelopmental disorders. This is due in large part to the unique features of zebrafish that make them an optimal system for this purpose, including rapid, external development of transparent embryos, which enable the direct visualization of the developing nervous system during early stages, large progenies, which provide considerable tractability for performing high-throughput pharmacological screens to identify small molecule suppressors of simple behavioral phenotypes, and ease of genetic manipulation, which has been greatly facilitated by the advent of CRISPR/Cas9 gene editing technologies. This review article focuses on studies that have harnessed these advantages of the zebrafish system for the functional analysis of genes that are strongly associated with the following neurodevelopmental disorders: autism spectrum disorders (ASD), epilepsy, intellectual disability (ID) and schizophrenia. We focus primarily on studies describing early morphological and behavioral phenotypes during embryonic and larval stages resulting from loss of risk gene function. We highlight insights into basic mechanisms of risk gene function gained from these studies as well as limitations of studies to date. Finally, we discuss advances in in vivo neural circuit imaging in zebrafish, which promise to transform research using the zebrafish model by illuminating novel circuit-level mechanisms with relevance to neurodevelopmental disorders.

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Section: Introductionmentioning

confidence: 99%

Zebrafish Models of Neurodevelopmental Disorders: Past, Present, and Future

Sakai

Ijaz

Hoffman

2018

Front. Mol. Neurosci.

127

123

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“…We determined that ~50 fish are needed per genotype in order to detect a >4% change between groups for morphometric features at 5 dpf at 80% power using our 'optimized' assay, though for certain traits (OT and Tel) far fewer fish are required (Table S2, Figure S4). and behavioral (average movement for the entire one h and the final 15 min following flashing lights) measurements for 5 dpf larvae for fish not subjected (0) and subjected (1) to VAST measurements at 3 dpf are shown as boxplots. Behavior was also plotted at varied PTZ concentrations (red=0 mM and blue=10 mM).…”

Section: Optimization Of a Combined Morphological And Behavioral Phenmentioning

confidence: 99%

“…Zebrafish (Danio rerio) are freshwater teleost fish widely used to study genes important in human diseases and traits, including neurological disorders such as autism-spectrum disorder (ASD; see review from [1]), intellectual disability (ID), and epilepsy (see review from [2,3]).…”

Section: Introductionmentioning

confidence: 99%

“…High-throughput zebrafish larvae phenotyping platform. (A) Impact of morphometric (L, EA, Tel, OT) and behavioral (average movement for the entire one h and the of final min following flashing lights) measurements for 5 dpf larvae for fish not subjected (0) and subjected(1) to VAST measurements at 3 dpf are shown as boxplots. Behavior was also plotted at varied PTZ concentrations (red=0 mM and blue=10 mM).…”

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Assessment of autism zebrafish mutant models using a high-throughput larval phenotyping platform

Colón-Rodríguez

Uribe-Salazar²,

Weyenberg³

et al. 2020

Preprint

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In recent years zebrafish have become commonly used as a model for studying human traits and disorders. Their small size, high fecundity, and rapid development allow for more high-throughput experiments compared to other vertebrate models. Given that zebrafish share >70% gene homologs with humans and their genomes can be readily edited using highly efficient CRISPR methods, we are now able to rapidly generate mutations impacting practically any gene of interest. Unfortunately, our ability to phenotype mutant larvae has not kept pace. To address this challenge, we have developed a protocol that obtains multiple phenotypic measurements from individual zebrafish larvae in an automated and parallel fashion, including morphological features (i.e., body length, eye area, and head size) and movement/behavior. By assaying wild-type zebrafish in a variety of conditions, we determined optimal parameters that avoid significant developmental defects or physical damage; these include morphological imaging of larvae at two time points (3 days post fertilization (dpf) and 5 dpf) coupled with motion tracking of behavior at 5 dpf. As a proof-of-principle, we tested our approach on two novel CRISPR-generated mutant zebrafish lines carrying predicted null-alleles of syngap1b and slc7a5, orthologs to two human genes implicated in autism-spectrum disorder, intellectual disability, and epilepsy. Using our optimized high-throughput phenotyping protocol, we recapitulated previously published results from mouse and zebrafish models of these candidate genes. In summary, we describe a rapid parallel pipeline to characterize morphological and behavioral features of individual larvae in a robust and consistent fashion, thereby improving our ability to better identify genes important in human traits and disorders.AUTHOR SUMMARYZebrafish (Danio rerio) are a well-established model organism for the study of neurodevelopmental disorders. Due to their small size, fast reproduction, and genetic homology with humans, zebrafish have been widely used for characterizing and screening candidate genes for many disorders, including autism-spectrum disorder, intellectual disability, and epilepsy. Although several studies have described the use of high-throughput morphological and behavioral assays, few combine multiple assays in a single zebrafish larva. Here, we optimized a platform to characterize morphometric features at two developmental time points in addition to behavioral traits of zebrafish larvae. We then used this approach to characterize two autism candidate genes (SYNGAP1 and SLC7A5) in two CRISPR-generated zebrafish null mutant models we developed in house. These data recapitulate previously published results related to enhanced seizure activity, while identifying additional defects not previously reported. We propose that our phenotyping platform represents a feasible method for maximizing the use of single zebrafish larvae in the characterization of additional mutants relevant to neurodevelopmental disorders.

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“…Regarding the zebrafish models of autism, zebrafish models own structures capable to display symptoms of The general biological relevance of the oxidative stress status in replicating some neuropsychiatric and digestive in zebrafish 573 ASD, being a useful tool for studying it (C. SHEN and Z. ZUO [18]; D.A.N. MESHALKINA & al [19]). Being social organisms, zebrafish models have been used to modulate behavioral symptoms of ASD through chemical substances intake as valproic acid (VPA) and several pesticides (D.A.N.…”

Section: Autism Spectrum Disordermentioning

confidence: 99%

The general biological relevance of the oxidative stress status in replicating some neuropsychiatric and digestive – related manifestations in zebrafish

Robea¹,

Săvucă²,

Strungaru³

et al. 2019

Rom Biotechnol Lett.

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Considering the awareness regarding the oxidative stress status implication in most of the actual neuropsychiatric disorders and also the ever increasing importance of zebrafish studies in this context, in the present paper we were interested in the general biological relevance of the oxidative stress status in replicating some neuropsychiatric manifestations in zebrafish, by focusing on the autism spectrum disorder, schizophrenia and Alzheimer's disease. Also considering the increased relevance of sleep-related studies in the neuropsychiatric pathology and the existence of some intriguing sleep studies in zebrafish, as well as the correlations between some digestive-related disorders such as irritable bowel syndrome and the neuropsychiatric aspects, some of these correlations and the possibility of studying them on zebrafish are also discussed and speculated during this mini-review.

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Zebrafish models of autism spectrum disorder

Cited by 116 publications

References 124 publications

Zebrafish Models of Neurodevelopmental Disorders: Past, Present, and Future

Zebrafish Models of Neurodevelopmental Disorders: Past, Present, and Future

Assessment of autism zebrafish mutant models using a high-throughput larval phenotyping platform

The general biological relevance of the oxidative stress status in replicating some neuropsychiatric and digestive – related manifestations in zebrafish

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