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Transcriptional effects of psychoactive drugs on genes involved in neurogenesis

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Version 2 2024-05-30, 14:35
Version 1 2020-11-10, 08:08
journal contribution
posted on 2024-06-19, 00:06 authored by CC Bortolasci, Briana RandallBriana Randall, S Kidnapillai, Timothy ConnorTimothy Connor, TTT Truong, Zoe Liu, B Panizzutti, Mark Richardson, Laura GrayLaura Gray, Michael BerkMichael Berk, Olivia DeanOlivia Dean, Ken WalderKen Walder
Although 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 Sciences

Volume

21

Article number

ARTN 8333

Pagination

1-19

Location

Switzerland

Open access

  • Yes

ISSN

1661-6596

eISSN

1422-0067

Language

English

Publication classification

C Journal article, C1 Refereed article in a scholarly journal

Copyright notice

2020, The Authors

Issue

21

Publisher

MDPI