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Download fileTranscriptional effects of psychoactive drugs on genes involved in neurogenesis
journal contribution
posted on 2020-11-01, 00:00 authored by Chiara BortolasciChiara Bortolasci, Briana RandallBriana Randall, Srisaiyini Kidnapillai, Timothy ConnorTimothy Connor, Thi Thuy Trang TruongThi Thuy Trang Truong, Zoe LiuZoe Liu, Bruna Panizzutti ParryBruna Panizzutti Parry, Mark RichardsonMark Richardson, Laura GrayLaura Gray, Michael BerkMichael Berk, Olivia DeanOlivia Dean, Ken WalderKen WalderAlthough neurogenesis is affected in several psychiatric diseases, the effects and mechanisms of action of psychoactive drugs on neurogenesis remain unknown and/or controversial. This study aims to evaluate the effects of psychoactive drugs on the expression of genes involved in neurogenesis. Neuronal-like cells (NT2-N) were treated with amisulpride (10 µM), aripiprazole (0.1 µM), clozapine (10 µM), lamotrigine (50 µM), lithium (2.5 mM), quetiapine (50 µM), risperidone (0.1 µM), or valproate (0.5 mM) for 24 h. Genome wide mRNA expression was quantified and analysed using gene set enrichment analysis, with the neurogenesis gene set retrieved from the Gene Ontology database and the Mammalian Adult Neurogenesis Gene Ontology (MANGO) database. Transcription factors that are more likely to regulate these genes were investigated to better understand the biological processes driving neurogenesis. Targeted metabolomics were performed using gas chromatography-mass spectrometry. Six of the eight drugs decreased the expression of genes involved in neurogenesis in both databases. This suggests that acute treatment with these psychoactive drugs negatively regulates the expression of genes involved in neurogenesis in vitro. SOX2 and three of its target genes (CCND1, BMP4, and DKK1) were also decreased after treatment with quetiapine. This can, at least in part, explain the mechanisms by which these drugs decrease neurogenesis at a transcriptional level in vitro. These results were supported by the finding of increased metabolite markers of mature neurons following treatment with most of the drugs tested, suggesting increased proportions of mature relative to immature neurons consistent with reduced neurogenesis.
History
Journal
International Journal of Molecular SciencesVolume
21Issue
21Article number
8333Publisher
MDPI AGLocation
Basel, SwitzerlandPublisher DOI
Link to full text
eISSN
1422-0067Language
engPublication classification
C Journal article; C1 Refereed article in a scholarly journalCopyright notice
2020, The AuthorsUsage metrics
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Categories
Keywords
neurogenesispsychotropic drugsneuronsbipolar disorderschizophreniapsychiatrymental healthneuroscienceScience & TechnologyLife Sciences & BiomedicinePhysical SciencesBiochemistry & Molecular BiologyChemistry, MultidisciplinaryChemistryNEURAL STEM-CELLSHIPPOCAMPAL NEUROGENESISANTIPSYCHOTIC TREATMENTADULTLITHIUMEXPRESSIONINCREASEDIFFERENTIATION