PUBLICATION
Clozapine-induced transcriptional changes in the zebrafish brain
- Authors
- Viana, J., Wildman, N., Hannon, E., Farbos, A., Neill, P.O., Moore, K., van Aerle, R., Paull, G., Santos, E., Mill, J.
- ID
- ZDB-PUB-200207-14
- Date
- 2020
- Source
- NPJ schizophrenia 6: 3 (Journal)
- Registered Authors
- Santos, Eduarda, Viana, Joana
- Keywords
- none
- MeSH Terms
- none
- PubMed
- 32015324 Full text @ NPJ Schizophr
Citation
Viana, J., Wildman, N., Hannon, E., Farbos, A., Neill, P.O., Moore, K., van Aerle, R., Paull, G., Santos, E., Mill, J. (2020) Clozapine-induced transcriptional changes in the zebrafish brain. NPJ schizophrenia. 6:3.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping