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Transcriptional Effects of Psychoactive Drugs on Genes Involved in Neurogenesis
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. Neuron...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672551/ https://www.ncbi.nlm.nih.gov/pubmed/33172123 http://dx.doi.org/10.3390/ijms21218333 |
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author | Bortolasci, Chiara C. Spolding, Briana Kidnapillai, Srisaiyini Connor, Timothy Truong, Trang T.T. Liu, Zoe S.J. Panizzutti, Bruna Richardson, Mark F. Gray, Laura Berk, Michael Dean, Olivia M. Walder, Ken |
author_facet | Bortolasci, Chiara C. Spolding, Briana Kidnapillai, Srisaiyini Connor, Timothy Truong, Trang T.T. Liu, Zoe S.J. Panizzutti, Bruna Richardson, Mark F. Gray, Laura Berk, Michael Dean, Olivia M. Walder, Ken |
author_sort | Bortolasci, Chiara C. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7672551 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76725512020-11-19 Transcriptional Effects of Psychoactive Drugs on Genes Involved in Neurogenesis Bortolasci, Chiara C. Spolding, Briana Kidnapillai, Srisaiyini Connor, Timothy Truong, Trang T.T. Liu, Zoe S.J. Panizzutti, Bruna Richardson, Mark F. Gray, Laura Berk, Michael Dean, Olivia M. Walder, Ken Int J Mol Sci Article 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. MDPI 2020-11-06 /pmc/articles/PMC7672551/ /pubmed/33172123 http://dx.doi.org/10.3390/ijms21218333 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bortolasci, Chiara C. Spolding, Briana Kidnapillai, Srisaiyini Connor, Timothy Truong, Trang T.T. Liu, Zoe S.J. Panizzutti, Bruna Richardson, Mark F. Gray, Laura Berk, Michael Dean, Olivia M. Walder, Ken Transcriptional Effects of Psychoactive Drugs on Genes Involved in Neurogenesis |
title | Transcriptional Effects of Psychoactive Drugs on Genes Involved in Neurogenesis |
title_full | Transcriptional Effects of Psychoactive Drugs on Genes Involved in Neurogenesis |
title_fullStr | Transcriptional Effects of Psychoactive Drugs on Genes Involved in Neurogenesis |
title_full_unstemmed | Transcriptional Effects of Psychoactive Drugs on Genes Involved in Neurogenesis |
title_short | Transcriptional Effects of Psychoactive Drugs on Genes Involved in Neurogenesis |
title_sort | transcriptional effects of psychoactive drugs on genes involved in neurogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672551/ https://www.ncbi.nlm.nih.gov/pubmed/33172123 http://dx.doi.org/10.3390/ijms21218333 |
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