Understanding neurobehavioral genetics of zebrafish (original) (raw)

Molecular psychiatry of zebrafish

Molecular psychiatry, 2015

Due to their well-characterized neural development and high genetic homology to mammals, zebrafish (Danio rerio) have emerged as a powerful model organism in the field of biological psychiatry. Here, we discuss the molecular psychiatry of zebrafish, and its implications for translational neuroscience research and modeling central nervous system (CNS) disorders. In particular, we outline recent genetic and technological developments allowing for in vivo examinations, high-throughput screening and whole-brain analyses in larval and adult zebrafish. We also summarize the application of these molecular techniques to the understanding of neuropsychiatric disease, outlining the potential of zebrafish for modeling complex brain disorders, including attention-deficit/hyperactivity disorder (ADHD), aggression, post-traumatic stress and substance abuse. Critically evaluating the advantages and limitations of larval and adult fish tests, we suggest that zebrafish models become a rapidly emergi...

Mutant and Transgenic Zebrafish in Modeling Neurobehavioral Disorders

Zebrafish have traditionally been used as effective genetic and developmental models in biomedical research. Recently, the scope and utility of zebrafish in biomedical research has been further expanded with the implementation of new genetic techniques aimed at developing translational models of human pathogenesis. Additionally, screens measuring specific neurobehavioral and developmental phenotypes have proven to be very robust. This chapter further discusses the utility of zebrafish in biomedical research and highlights some of the genetic techniques used in the creation of transgenic and mutant strains. Behavioral phenotypes of genetically altered zebrafish are also discussed with respect to both their robust stress responses and similarity to human disorders. Specific emphasis is placed on human brain pathogenesis and neurodevelopmental abnormalities, especially as they relate to stress and anxiety spectrum disorders.

The role of zebrafish (Danio rerio) in dissecting the genetics and neural circuits underlying complex behavioural phenotypes

Zebrafish have great potential to contribute to our understanding of behavioral genetics and thus to contribute to our understanding of the etiology of psychiatric disease. However, progress is dependent upon the rate at which behavioral assays addressing complex behavioral phenotypes are designed, reported and validated. Here we critically review existing behavioral assays with particular focus on the use of adult zebrafish to explore executive processes and phenotypes associated with human psychiatric disease. We outline the case for using zebrafish as models to study impulse control and attention, discussing the validity of applying extant rodent assays to zebrafish and evidence for the conservation of relevant neural circuits.

Zebrafish as a Model of Neurodevelopmental Disorders

Neuroscience, 2019

Neurodevelopmental disorders (NDDs) caused by aberrant brain growth and development are lifelong , debilitating illnesses that markedly impair the quality of life. Animal models are a valuable tool for studying NDD pathobiology and therapies. Mounting evidence suggests the zebrafish (Danio rerio) as a useful model organism to study NDDs with high physiological homology to humans and sensitivity to pharmacological and genetic manipulations. Here, we summarize experimental models of NDDs in zebrafish and highlight the growing translational significance of zebrafish NDD-related phenotypes. We also emphasize the need in further development of zebrafish models of NDDs to improve our understanding of their pathogenesis and therapeutic treatments.

The role of zebrafish (Danio rerio) in dissecting the genetics and neural circuits of executive function

Zebrafish have great potential to contribute to our understanding of behavioral genetics and thus to contribute to our understanding of the etiology of psychiatric disease. However, progress is dependent upon the rate at which behavioral assays addressing complex behavioral phenotypes are designed, reported and validated. Here we critically review existing behavioral assays with particular focus on the use of adult zebrafish to explore executive processes and phenotypes associated with human psychiatric disease. We outline the case for using zebrafish as models to study impulse control and attention, discussing the validity of applying extant rodent assays to zebrafish and evidence for the conservation of relevant neural circuits.

Larval Zebrafish as a Model for Mechanistic Discovery in Mental Health

Frontiers in Molecular Neuroscience

Animal models are essential for the discovery of mechanisms and treatments for neuropsychiatric disorders. However, complex mental health disorders such as depression and anxiety are difficult to fully recapitulate in these models. Borrowing from the field of psychiatric genetics, we reiterate the framework of ‘endophenotypes’ – biological or behavioral markers with cellular, molecular or genetic underpinnings – to reduce complex disorders into measurable behaviors that can be compared across organisms. Zebrafish are popular disease models due to the conserved genetic, physiological and anatomical pathways between zebrafish and humans. Adult zebrafish, which display more sophisticated behaviors and cognition, have long been used to model psychiatric disorders. However, larvae (up to 1 month old) are more numerous and also optically transparent, and hence are particularly suited for high-throughput screening and brain-wide neural circuit imaging. A number of behavioral assays have be...

Zebrafish models in neuropsychopharmacology and CNS drug discovery

British Journal of Pharmacology

Despite the high prevalence of neuropsychiatric disorders, their aetiology and molecular mechanisms remain poorly understood. The zebrafish (Danio rerio) is increasingly utilized as a powerful animal model in neuropharmacology research and in vivo drug screening. Collectively, this makes zebrafish a useful tool for drug discovery and the identification of disordered molecular pathways. Here, we discuss zebrafish models of selected human neuropsychiatric disorders and drug-induced phenotypes. As well as covering a broad range of brain disorders (from anxiety and psychoses to neurodegeneration), we also summarize recent developments in zebrafish genetics and small molecule screening, which markedly enhance the disease modelling and the discovery of novel drug targets.

A Mini-Review Regarding the Modalities to Study Neurodevelopmental Disorders-Like Impairments in Zebrafish—Focussing on Neurobehavioural and Psychological Responses

Brain Sciences

Neurodevelopmental disorders (NDDs) are complex disorders which can be associated with many comorbidities and exhibit multifactorial-dependent phenotypes. An important characteristic is represented by the early onset of the symptoms, during childhood or young adulthood, with a great impact on the socio-cognitive functioning of the affected individuals. Thus, the aim of our review is to describe and to argue the necessity of early developmental stages zebrafish models, focusing on NDDs, especially autism spectrum disorders (ASD) and also on schizophrenia. The utility of the animal models in NDDs or schizophrenia research remains quite controversial. Relevant discussions can be opened regarding the specific characteristics of the animal models and the relationship with the etiologies, physiopathology, and development of these disorders. The zebrafish models behaviors displayed as early as during the pre-hatching embryo stage (locomotor activity prone to repetitive behavior), and post-...

The developing utility of zebrafish in modeling neurobehavioral disorders

2010

The developing utility of zebrafish in modeling neurobehavioral disorders. A Stewart, F Kadri, J DiLeo, K Chung, J Cachat, J Goodspeed, C Suciu, S Roy, S Gaikwad, K Wong, M Elegante, S Elkhayat, N Wu, T Gilder, D Tien, L Grossman, J Tan, A Denmark, B Bartels, K Frank, E Beeson, AV Kalueff Int J Comp Psychol 23:11, 104-121, 2010.

Current State of Modeling Human Psychiatric Disorders Using Zebrafish

International Journal of Molecular Sciences

Psychiatric disorders are highly prevalent brain pathologies that represent an urgent, unmet biomedical problem. Since reliable clinical diagnoses are essential for the treatment of psychiatric disorders, their animal models with robust, relevant behavioral and physiological endpoints become necessary. Zebrafish (Danio rerio) display well-defined, complex behaviors in major neurobehavioral domains which are evolutionarily conserved and strikingly parallel to those seen in rodents and humans. Although zebrafish are increasingly often used to model psychiatric disorders, there are also multiple challenges with such models as well. The field may therefore benefit from a balanced, disease-oriented discussion that considers the clinical prevalence, the pathological complexity, and societal importance of the disorders in question, and the extent of its detalization in zebrafish central nervous system (CNS) studies. Here, we critically discuss the use of zebrafish for modeling human psychi...