The zebrafish as a promising tool for modeling human brain disorders: A review based upon an IBNS Symposium

Abstract

The zebrafish represents an excellent compromise between system complexity and practical simplicity, features that make it useful for modeling and mechanistic analysis of complex brain disorders. Also promising are screens for psychoactive drugs with effects on larval and adult zebrafish behavior. This review, based upon a recent symposium held at the 2016 IBNS Congress, provides different perspectives on how the zebrafish may be utilized to advance research into human central nervous system disorders. It starts with a discussion on an important bottleneck in zebrafish research, measuring the behavior of this species (specifically shoaling), and continues with examples on research on autism spectrum disorder in larval zebrafish, on screening natural products for compounds with psychoactive properties in adult zebrafish, and on the development of a zebrafish model of fetal alcohol spectrum disorders. By providing information on a broad spectrum of brain disorders, experimental methods, and scientific approaches using both larval and adult zebrafish, the review is intended to showcase this underutilized laboratory species for behavioral neuroscience and psychopharmacology research.

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

“…While there are cases where genetic compensation has been shown to occur in mutants (Rossi et al, 2015; El-Brolosy and Stainier, 2017), the current guidelines require demonstrating the absence of the morpholino-induced phenotype in the mutant background as evidence for compensation (Stainier et al, 2017). Moving forward, following these guidelines will be critical, particularly for the interpretation of phenotypes in zebrafish models of neurodevelopmental disorders, given that morpholinos alone can induce nonspecific neural effects (Shams et al, 2018). At the same time, as mutants become the “gold standard” for reverse genetics studies in zebrafish, it will be equally important to confirm that germline mutations result in loss-of-function (Shams et al, 2018).…”

“…Moving forward, following these guidelines will be critical, particularly for the interpretation of phenotypes in zebrafish models of neurodevelopmental disorders, given that morpholinos alone can induce nonspecific neural effects (Shams et al, 2018). At the same time, as mutants become the “gold standard” for reverse genetics studies in zebrafish, it will be equally important to confirm that germline mutations result in loss-of-function (Shams et al, 2018). …”

“…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.…”

Sensory ecology of ostariophysan alarm substances

“…These two research traditions rarely cross‐fertilized each other; however, good ethological validation, ecological relevance and adequate knowledge of the neural bases of a given behavioural function are crucial for its use as a model system in the behavioural neurosciences and neuropharmacology (van der Staay, ; Maximino & van der Staay, ). As a result, and as a consequence of the ascension of D. rerio as a model organism in the field (Kalueff et al ., ; Shams et al ., ; Stewart, Yang, et al ., ), more focus has been given on the applications of CAS as an aversive stimulus in many different paradigms, from aversive conditioning (Maximino et al ., ; Ruhl et al ., ) to behavioural models in psychopathology (§ 5).…”

The Integration of Sociality, Monoamines, and Stress Neuroendocrinology in Fish Models: Applications in the Neurosciences

“…The zebrafish has been proposed to model such disorders to facilitate discovery of their mechanisms and development of treatment (Kalueff et al, 2014;Stewart et al, 2015;Shams et al, 2018). However, this type of research suffers from an inherent paradox: in order for one to properly model the chosen human disorder, one has to first know its mechanism, the latter being the reason why the disease model would be created at the first place.…”