Journal article
Drugs used to treat bipolar disorder act via microRNAs to regulate expression of genes involved in neurite outgrowth
Journal of psychopharmacology, Vol.34(3), pp.370-379
03/2020
PMID: 31913086
Metrics
1 Record Views
Abstract
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<0.05.
Results: We found that bipolar disorder drugs tended to increase the expression of miR-128 and miR-378 (p<0.05). Putative target genes of these microRNAs targeted pathways including those identified as “neuron projection development” and “axonogenesis”. Many of the target genes are inhibitors of neurite outgrowth and neurogenesis and were downregulated following bipolar disorder drug combination treatment (all p<0.05). The bipolar disorder drug combination tended to decrease the expression of the target genes (NOVA1, GRIN3A, and VIM), however this effect could be reversed by the application of microRNA inhibitors.
Conclusions: We conclude that at a transcriptional level, bipolar disorder drugs affect several genes in concert that would increase neurite outgrowth and neurogenesis and hence neural plasticity, and that this effect is mediated (at least in part) by modulation of the expression of these two key microRNAs.
Details
- Title
- Drugs used to treat bipolar disorder act via microRNAs to regulate expression of genes involved in neurite outgrowth
- Creators
- Srisaiyini Kidnapillai - Deakin University (Australia, Geelong)Ben Wade - Deakin University (Australia, Geelong)Chiara C Bortolasci - Deakin University (Australia, Geelong)Bruna Panizzutti - Universidade Federal do Rio Grande do SulBriana Spolding - Deakin University (Australia, Geelong)Timothy Connor - Deakin University (Australia, Geelong)Tamsyn Crowley - Deakin University (Australia, Geelong)Stéphane Jamain - Université Paris-Est CréteilLaura Gray - Deakin University (Australia, Geelong)Marion Leboyer - Université Paris-Est CréteilMichael Berk - Florey Institute of Neuroscience and Mental HealthKen Walder - Deakin University (Australia, Geelong)
- Publication Details
- Journal of psychopharmacology, Vol.34(3), pp.370-379
- Publisher
- SAGE Publications
- Identifiers
- 991013328528102368
- Copyright
- © The Author(s) 2020.
- Academic Unit
- Office of Senior Deputy Vice Chancellor, Research
- Language
- English
- Resource Type
- Journal article