Zebrafish Modeling of Autism Spectrum Disorders, Current Status and Future Prospective

Abstract

Autism spectrum disorder (ASD) refers to a complicated range of childhood neurodevelopmental disorders which can occur via genetic or non-genetic factors. Clinically, ASD is associated with problems in relationships, social interactions, and behaviors that pose many challenges for children with ASD and their families. Due to the complexity, heterogeneity, and association of symptoms with some neuropsychiatric disorders such as ADHD, anxiety, and sleep disorders, clinical trials have not yielded reliable results and there still remain challenges in drug discovery and development pipeline for ASD patients. One of the main steps in promoting lead compounds to the suitable drug for commercialization is preclinical animal testing, in which the efficacy and toxicity of candidate drugs are examined in vivo. In recent years, zebrafish have been able to attract the attention of many researchers in the field of neurological disorders such as ASD due to their outstanding features. The presence of orthologous genes for ASD modeling, the anatomical similarities of parts of the brain, and similar neurotransmitter systems between zebrafish and humans are some of the main reasons why scientists draw attention to zebrafish as a prominent animal model in preclinical studies to discover highly effective treatment approaches for the ASD through genetic and non-genetic modeling methods.

The Risk Genes for Neuropsychiatric Disorders negr1 and opcml Are Expressed throughout Zebrafish Brain Development

“…Notably, some of these domains have been linked to neuropsychiatric disorders which both genes have been implicated in, such as major depressive disorder (MDD), schizophrenia [ 27 , 28 ], and autism spectrum disorder (ASD) [ 27 , 28 , 33 ]. For instance, negr1 and opcml are strongly expressed in the zebrafish pallium, which has been proposed to harbour structures homologous to the hippocampus and amygdala of mammals [ 50 ] involved in ASD and schizophrenia [ 51 ]. NEGR1 −/− mice exhibit a reduced volume of brain regions, including the hippocampus.…”

Understanding CNS Effects of Antimicrobial Drugs Using Zebrafish Models

“…Zebrafish also exhibit a wide range of well-described behaviors, allowing the study of drug effects on locomotor, anxiety- and depression-like, and social phenotypes [ 75 , 76 , 77 ]. Collectively, this enables the use of zebrafish in translational modeling of neurodegenerative, affective, psychotic, neurodevelopmental, and addictive disorders [ 4 , 78 , 79 ].…”

Oxytocin Enhances Time-Dependent Responses in the Aggressive Zebrafish (Danio rerio)

“…Since its first use in the 1970s by George Streisinger, zebrafish has contributed to the present knowledge, mostly because of the advantages it possesses such as a transparent embryo stage, external fertilization, rapid development, high fecundity, easy genetic manipulation, and a fully sequenced genome, among others [ 15 , 16 ]. There are numerous reports that describe the involvement of zebrafish in ASD modeling for mechanisms and therapeutic intervention studies [ 10 , 17 ]. Zebrafish have a high repertoire of behaviors that are extensively studied, especially those that are strongly connected to the disorder.…”