Clozapine-induced Transcriptional Changes in the Zebrafish Brain

Overview

Journal NPJ Schizophr

Date 2020 Feb 5

PMID 32015324

Citations 4

Authors

Joana Viana

Nick Wildman

Eilis Hannon

Audrey Farbos

Paul O Neill

Karen Moore

Ronny van Aerle

Greg Paull

Eduarda Santos

Jonathan Mill

Affiliations

Soon will be listed here.

Abstract

Clozapine is an atypical antipsychotic medication that is used to treat schizophrenia patients who are resistant to other antipsychotic drugs. The molecular mechanisms mediating the effects of clozapine are not well understood and its use is often associated with severe side-effects. In this study, we exposed groups of wild-type zebrafish to two doses of clozapine ('low' (20 µg/L) and 'high' (70 µg/L)) over a 72-h period, observing dose-dependent effects on behaviour. Using RNA sequencing (RNA-seq) we identified multiple genes differentially expressed in the zebrafish brain following exposure to clozapine. Network analysis identified co-expression modules characterised by striking changes in module connectivity in response to clozapine, and these were enriched for regulatory pathways relevant to the etiology of schizophrenia. Our study highlights the utility of zebrafish as a model for assessing the molecular consequences of antipsychotic medications and identifies genomic networks potentially involved in schizophrenia.

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