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Larval Zebrafish as a Model for Mechanistic Discovery in Mental Health

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 f...

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Autores principales: Tan, Jazlynn Xiu Min, Ang, Ryan Jun Wen, Wee, Caroline Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263853/
https://www.ncbi.nlm.nih.gov/pubmed/35813062
http://dx.doi.org/10.3389/fnmol.2022.900213
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author Tan, Jazlynn Xiu Min
Ang, Ryan Jun Wen
Wee, Caroline Lei
author_facet Tan, Jazlynn Xiu Min
Ang, Ryan Jun Wen
Wee, Caroline Lei
author_sort Tan, Jazlynn Xiu Min
collection PubMed
description 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 been developed to quantify neuropsychiatric phenomena in larval zebrafish. Here, we will review these assays and the current knowledge regarding the underlying mechanisms of their behavioral readouts. We will also discuss the existing evidence linking larval zebrafish behavior to specific human behavioral traits and how the endophenotype framework can be applied. Importantly, many of the endophenotypes we review do not solely define a diseased state but could manifest as a spectrum across the general population. As such, we make the case for larval zebrafish as a promising model for extending our understanding of population mental health, and for identifying novel therapeutics and interventions with broad impact.
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spelling pubmed-92638532022-07-09 Larval Zebrafish as a Model for Mechanistic Discovery in Mental Health Tan, Jazlynn Xiu Min Ang, Ryan Jun Wen Wee, Caroline Lei Front Mol Neurosci 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 been developed to quantify neuropsychiatric phenomena in larval zebrafish. Here, we will review these assays and the current knowledge regarding the underlying mechanisms of their behavioral readouts. We will also discuss the existing evidence linking larval zebrafish behavior to specific human behavioral traits and how the endophenotype framework can be applied. Importantly, many of the endophenotypes we review do not solely define a diseased state but could manifest as a spectrum across the general population. As such, we make the case for larval zebrafish as a promising model for extending our understanding of population mental health, and for identifying novel therapeutics and interventions with broad impact. Frontiers Media S.A. 2022-06-24 /pmc/articles/PMC9263853/ /pubmed/35813062 http://dx.doi.org/10.3389/fnmol.2022.900213 Text en Copyright © 2022 Tan, Ang and Wee. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Tan, Jazlynn Xiu Min
Ang, Ryan Jun Wen
Wee, Caroline Lei
Larval Zebrafish as a Model for Mechanistic Discovery in Mental Health
title Larval Zebrafish as a Model for Mechanistic Discovery in Mental Health
title_full Larval Zebrafish as a Model for Mechanistic Discovery in Mental Health
title_fullStr Larval Zebrafish as a Model for Mechanistic Discovery in Mental Health
title_full_unstemmed Larval Zebrafish as a Model for Mechanistic Discovery in Mental Health
title_short Larval Zebrafish as a Model for Mechanistic Discovery in Mental Health
title_sort larval zebrafish as a model for mechanistic discovery in mental health
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263853/
https://www.ncbi.nlm.nih.gov/pubmed/35813062
http://dx.doi.org/10.3389/fnmol.2022.900213
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