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dc.contributor.authorBortolasci, CC
dc.contributor.authorSpolding, B
dc.contributor.authorKidnapillai, S
dc.contributor.authorConnor, T
dc.contributor.authorTruong, TTT
dc.contributor.authorLiu, ZSJ
dc.contributor.authorPanizzutti, B
dc.contributor.authorRichardson, MF
dc.contributor.authorGray, L
dc.contributor.authorBerk, M
dc.contributor.authorDean, OM
dc.contributor.authorWalder, K
dc.date.accessioned2020-12-09T22:34:38Z
dc.date.available2020-12-09T22:34:38Z
dc.date.issued2020-11-01
dc.identifierpii: ijms21218333
dc.identifier.citationBortolasci, C. C., Spolding, B., Kidnapillai, S., Connor, T., Truong, T. T. T., Liu, Z. S. J., Panizzutti, B., Richardson, M. F., Gray, L., Berk, M., Dean, O. M. & Walder, K. (2020). Transcriptional Effects of Psychoactive Drugs on Genes Involved in Neurogenesis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21 (21), https://doi.org/10.3390/ijms21218333.
dc.identifier.issn1422-0067
dc.identifier.urihttp://hdl.handle.net/11343/253006
dc.description.abstractAlthough 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.
dc.languageEnglish
dc.publisherMDPI
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleTranscriptional Effects of Psychoactive Drugs on Genes Involved in Neurogenesis
dc.typeJournal Article
dc.identifier.doi10.3390/ijms21218333
melbourne.affiliation.departmentPsychiatry
melbourne.source.titleInternational Journal of Molecular Sciences
melbourne.source.volume21
melbourne.source.issue21
dc.rights.licenseCC BY
melbourne.elementsid1480283
melbourne.contributor.authorBerk, Michael
dc.identifier.eissn1422-0067
melbourne.accessrightsOpen Access


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