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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
The use of a gene expression signature and connectivity map to repurpose drugs for bipolar disorder
World Journal of Biological Psychiatry, Volume 21, No. 10, Year 2020
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Description
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. © 2018 Informa UK Limited, trading as Taylor & Francis Group.
Authors & Co-Authors
Kidnapillai, Srisaiyini
Australia, Geelong
Deakin University
Bortolasci, Chiara Cristina
Australia, Geelong
Deakin University
Panizzutti, B.
Brazil, Porto Alegre
Universidade Federal do Rio Grande do Sul
Spolding, Briana
Australia, Geelong
Deakin University
Connor, Timothy
Australia, Geelong
Deakin University
Sanigorski, Andrew M.
Australia, Geelong
Deakin University
Dean, Olívia May
Australia, Melbourne
The Florey
Australia, Geelong
Barwon Health
Australia, Melbourne
University of Melbourne
Crowley, Tamsyn M.
Australia, Geelong
Deakin University
Jamain, Stéphane
France, Creteil
Institut Mondor de Recherche Biomédicale
Gray, Laura J.
Australia, Geelong
Deakin University
Australia, Melbourne
The Florey
Leboyer, Marion
France, Creteil
Institut Mondor de Recherche Biomédicale
Berk, Michael
Australia, Melbourne
The Florey
Australia, Geelong
Barwon Health
Australia, Melbourne
University of Melbourne
Australia, Melbourne
Orygen Youth Health
Walder, Ken R.
Australia, Geelong
Deakin University
Statistics
Citations: 20
Authors: 13
Affiliations: 8
Identifiers
Doi:
10.1080/15622975.2018.1492734
ISSN:
15622975
Research Areas
Genetics And Genomics
Mental Health