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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 Parry, B, Richardson, Mark F., Gray, Laura, Berk, Michael, Dean, Olivia and Walder, Ken 2020, Transcriptional effects of psychoactive drugs on genes involved in neurogenesis, International Journal of Molecular Sciences, vol. 21, no. 21, doi: 10.3390/ijms21218333.

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Title Transcriptional effects of psychoactive drugs on genes involved in neurogenesis
Author(s) Bortolasci, Chiara C.ORCID iD for Bortolasci, Chiara C. orcid.org/0000-0002-0794-6363
Spolding, Briana
Kidnapillai, Srisaiyini
Connor, Timothy
Truong, Trang T. T.
Liu, Zoe S.J.
Panizzutti Parry, BORCID iD for Panizzutti Parry, B orcid.org/0000-0002-1650-0064
Richardson, Mark F.ORCID iD for Richardson, Mark F. orcid.org/0000-0002-1650-0064
Gray, LauraORCID iD for Gray, Laura orcid.org/0000-0002-7903-5796
Berk, MichaelORCID iD for Berk, Michael orcid.org/0000-0002-5554-6946
Dean, OliviaORCID iD for Dean, Olivia orcid.org/0000-0002-2776-3935
Walder, KenORCID iD for Walder, Ken orcid.org/0000-0002-6758-4763
Journal name International Journal of Molecular Sciences
Volume number 21
Issue number 21
Article ID 8333
Total pages 19
Publisher MDPI AG
Place of publication Basel, Switzerland
Publication date 2020-11
ISSN 1422-0067
Keyword(s) bipolar disorder
mental health
neurogenesis
neurons
neuroscience
psychiatry
psychotropic drugs
schizophrenia
Summary 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.
Language eng
DOI 10.3390/ijms21218333
Indigenous content off
Field of Research 0399 Other Chemical Sciences
0604 Genetics
0699 Other Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2020, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30145091

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.