Journal article
The use of a gene expression signature and connectivity map to repurpose drugs for bipolar disorder
The world journal of biological psychiatry, Vol.21(10), pp.775-783
12/2020
PMID: 29956574
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Abstract
Objectives: To create a gene expression signature (GES) to represent the biological effects of a combination of known drugs for bipolar disorder (BD) on cultured human neuronal cells (NT2-N) and rat brains, which also has evidence of differential expression in individuals with BD. To use the GES to identify new drugs for BD using Connectivity Map (CMap).
Methods: NT2-N (n = 20) cells and rats ( n = 8) were treated with a BD drug combination (lithium, valproate, quetiapine and lamotrigine) or vehicle for 24 and 6 h, respectively. Following next-generation sequencing, the differential expression of genes was assessed using edgeR in R. The derived GES was compared to differentially expressed genes in post-mortem brains of individuals with BD. The GES was then used in CMap analysis to identify similarly acting drugs.
Results: A total of 88 genes showed evidence of differential expression in response to the drug combination in both models, and therefore comprised the GES. Six of these genes showed evidence of differential expression in post-mortem brains of individuals with BD. CMap analysis identified 10 compounds (camptothecin, chlorambucil, flupenthixol, valdecoxib, rescinnamine, GW-8510, cinnarizine, lomustine, mifepristone and nimesulide) acting similarly to the BD drug combination.
Conclusions: This study shows that GES and CMap can be used as tools to repurpose drugs for BD.
Details
- Title
- The use of a gene expression signature and connectivity map to repurpose drugs for bipolar disorder
- Creators
- Srisaiyini Kidnapillai - Deakin University (Australia, Geelong)Chiara C Bortolasci - Deakin University (Australia, Geelong)Madhara Udawela - Florey Institute of Neuroscience and Mental HealthBruna Panizzutti - Universidade Federal do Rio Grande do SulBriana Spolding - Deakin University (Australia, Geelong)Timothy Connor - Deakin University (Australia, Geelong)Andrew Sanigorski - Deakin University (Australia, Geelong)Olivia M Dean - Florey Institute of Neuroscience and Mental HealthTamsyn Crowley - Deakin University (Australia, Geelong)Stéphane Jamain - Université Paris-Est CréteilLaura Gray - Deakin University (Australia, Geelong)Elizabeth Scarr - Florey Institute of Neuroscience and Mental HealthMarion Leboyer - Université Paris-Est CréteilBrian Dean - Florey Institute of Neuroscience and Mental HealthMichael Berk - Florey Institute of Neuroscience and Mental HealthKen Walder - Deakin University (Australia, Geelong)
- Publication Details
- The world journal of biological psychiatry, Vol.21(10), pp.775-783
- Publisher
- Taylor & Francis
- Identifiers
- 991013328726902368
- Copyright
- © 2018 Informa UK Limited, trading as Taylor & Francis Group.
- Academic Unit
- Office of Senior Deputy Vice Chancellor, Research
- Language
- English
- Resource Type
- Journal article