Toward developmental models of psychiatric disorders in zebrafish

Abstract

Psychiatric disorders are a diverse set of diseases that affect all aspects of mental function including social interaction, thinking, feeling, and mood. Although psychiatric disorders place a large economic burden on society, the drugs available to treat them are often palliative with variable efficacy and intolerable side-effects. The development of novel drugs has been hindered by a lack of knowledge about the etiology of these diseases. It is thus necessary to further investigate psychiatric disorders using a combination of human molecular genetics, gene-by-environment studies, in vitro pharmacological and biochemistry experiments, animal models, and investigation of the non-biological basis of these diseases, such as environmental effects. Many psychiatric disorders, including autism spectrum disorder, attention-deficit/hyperactivity disorder, mental retardation, and schizophrenia can be triggered by alterations to neural development. The zebrafish is a popular model for developmental biology that is increasingly used to study human disease. Recent work has extended this approach to examine psychiatric disorders as well. However, since psychiatric disorders affect complex mental functions that might be human specific, it is not possible to fully model them in fish. In this review, I will propose that the suitability of zebrafish for developmental studies, and the genetic tools available to manipulate them, provide a powerful model to study the roles of genes that are linked to psychiatric disorders during neural development. The relative speed and ease of conducting experiments in zebrafish can be used to address two areas of future research: the contribution of environmental factors to disease onset, and screening for novel therapeutic compounds.

Unpredictable chronic stress decreases inhibitory avoidance learning in Tuebingen Long-Fin zebrafish (Danio rerio Hamilton): stronger effects in the resting phase than in the active phase

“…Our data strongly suggest that at a behavioural and physiological level the UCS protocol is robust and reproducible in decreasing inhibitory learning and elevating whole-body cortisol content across strains of zebrafish, i.e. the TLF strain used in our study and the AB strain in the study of Piato and colleagues (Piato et al, 2011), which is critical for advancing the zebrafish as a model for brain-behaviour studies associated with depression, anxiety and other mood-related disorders (Chakravarty et al, 2013;Gerlai, 2010a;Gerlai, 2010b;Norton, 2013;Piato et al, 2011). In addition, our data reveal that the reduction in inhibitory avoidance learning relates to increasing levels of stress load.…”

“…An upcoming research area is the use of zebrafish as a model to study the effects of chronic stress on brain and behaviour in relation to depression, anxiety and other mood-related disorders (Chakravarty et al, 2013;Gerlai, 2010a;Gerlai, 2010b;Norton, 2013;Piato et al, 2011;Stewart et al, 2014). Zebrafish may be of interest for chronic stress research as they express two glucocorticoid receptors (GR), GRα and GRβ, as humans do but not rodents (Schaaf et al, 2009;Schoonheim et al, 2010).…”

Zebrafish—on the move towards ophthalmological research

“…The large number of embryos produced per clutch makes zebrafish a prominent model for higher-throughput screening of small molecules, 9 which is mandatory for preclinical drug development and toxicity assessment. 10 So far, zebrafish have been used to model a wide variety of human diseases, including hereditary muscle diseases, 11 neurological disorders, 12 tuberculosis, 13 cancer, 14 cardiovascular diseases, 15 and haematopoietic and infectious diseases. 16 In addition, zebrafish are a valuable vertebrate model for studying vision-related disorders.…”

Zebrafish: a novel model in neuropsychopharmacological research

“…Hence it is imperative to further explore psychiatric disorders using a combination of human molecular genetics, in vitro pharmacological and biochemistry experiments, animal models, and investigation of the nonbiological basis of these diseases, such as environmental effects. 1 Furthermore, as the population ages, there is an increasing need for efficacious and safe therapies for the treatment of neurological diseases. A restricted number of treatment options are presently available to recover the cognitive dysfunction and research is limited by the need for in vivo models.…”