Drugs used to treat bipolar disorder act via microRNAs to regulate expression of genes involved in neurite outgrowth.
bipolar disorder
depression
mania
microRNAs
neurite outgrowth
next generation sequencing
Journal
Journal of psychopharmacology (Oxford, England)
ISSN: 1461-7285
Titre abrégé: J Psychopharmacol
Pays: United States
ID NLM: 8907828
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
pubmed:
9
1
2020
medline:
4
2
2021
entrez:
9
1
2020
Statut:
ppublish
Résumé
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. 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 ( We found that bipolar disorder drugs tended to increase the expression of miR-128 and miR-378 ( 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.
Sections du résumé
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 (
RESULTS
We found that bipolar disorder drugs tended to increase the expression of miR-128 and miR-378 (
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.
Identifiants
pubmed: 31913086
doi: 10.1177/0269881119895534
doi:
Substances chimiques
MIRN128 microRNA, human
0
MIRN378 microRNA, human
0
MicroRNAs
0
Quetiapine Fumarate
2S3PL1B6UJ
Valproic Acid
614OI1Z5WI
Lithium Chloride
G4962QA067
Lamotrigine
U3H27498KS
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM