Drugs used to treat bipolar disorder act via microRNAs to regulate expression of genes involved in neurite outgrowth

Background: The drugs commonly used to treat bipolar disorder have limited efficacy and drug discovery is hampered by the paucity of knowledge of the pathophysiology of this disease. This study aims to explore the role of microRNAs in bipolar disorder and understand the molecular mechanisms of actio...

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Bibliographic Details
Published in:Journal of psychopharmacology (Oxford) 2020-03, Vol.34 (3), p.370-379
Main Authors: Kidnapillai, Srisaiyini, Wade, Ben, Bortolasci, Chiara C, Panizzutti, Bruna, Spolding, Briana, Connor, Timothy, Crowley, Tamsyn, Jamain, Stéphane, Gray, Laura, Leboyer, Marion, Berk, Michael, Walder, Ken
Format: Article
Language:English
Subjects:
Axonogenesis
Bipolar disorder
Cells, Cultured
Drug Synergism
Drugs
Gene Expression - drug effects
Humans
Lamotrigine
Lamotrigine - pharmacology
Lithium
Lithium Chloride - pharmacology
MicroRNAs
MicroRNAs - biosynthesis
miRNA
Molecular modelling
Neurogenesis
Neuronal Outgrowth - genetics
Neuroplasticity
Next-generation sequencing
Quetiapine
Quetiapine Fumarate - pharmacology
Transcription
Valproic acid
Valproic Acid - pharmacology
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Summary:Background: The drugs commonly used to treat bipolar disorder have limited efficacy and drug discovery is hampered by the paucity of knowledge of the pathophysiology of this disease. This study aims to explore the role of microRNAs in bipolar disorder and understand the molecular mechanisms of action of commonly used bipolar disorder drugs. Methods: The transcriptional effects of bipolar disorder drug combination (lithium, valproate, lamotrigine and quetiapine) in cultured human neuronal cells were studied using next generation sequencing. Differential expression of genes (n=20) and microRNAs (n=6) was assessed and the differentially expressed microRNAs were confirmed with TaqMan MicroRNA Assays. The expression of the differentially expressed microRNAs were inhibited to determine bipolar disorder drug effects on their target genes (n=8). Independent samples t-test was used for normally distributed data and Kruskal-Wallis/Mann-Whitney U test was used for data not distributed normally. Significance levels were set at p
ISSN:0269-8811
1461-7285
DOI:10.1177/0269881119895534