Metergoline Shares Properties with Atypical Antipsychotic Drugs Identified by Gene Expression Signature Screen.

Autor: Bortolasci CC; The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia., Jaehne EJ; School of Psychology and Public Health, La Trobe University, Bundoora, Australia., Hernández D; The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia. d.hernandez@deakin.edu.au., Spolding B; The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia., Connor T; The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia., Panizzutti B; The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia., Dean OM; The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.; Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Melbourne, Australia., Crowley TM; The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia., Yung AR; The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.; School of Health Sciences, University of Manchester, Manchester, UK.; Centre for Youth Mental Health, University of Melbourne, Parkville, Australia., Gray L; The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.; Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Melbourne, Australia., Kim JH; The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.; Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Melbourne, Australia., van den Buuse M; School of Psychology and Public Health, La Trobe University, Bundoora, Australia., Berk M; The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia., Walder K; The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.
Jazyk: angličtina
Zdroj: Neurotoxicity research [Neurotox Res] 2023 Dec; Vol. 41 (6), pp. 502-513. Date of Electronic Publication: 2023 Nov 03.
DOI: 10.1007/s12640-023-00673-0
Abstrakt: Novel approaches are required to find new treatments for schizophrenia and other neuropsychiatric disorders. This study utilised a combination of in vitro transcriptomics and in silico analysis with the BROAD Institute's Connectivity Map to identify drugs that can be repurposed to treat psychiatric disorders. Human neuronal (NT2-N) cells were treated with a combination of atypical antipsychotic drugs commonly used to treat psychiatric disorders (such as schizophrenia, bipolar disorder, and major depressive disorder), and differential gene expression was analysed. Biological pathways with an increased gene expression included circadian rhythm and vascular endothelial growth factor signalling, while the adherens junction and cell cycle pathways were transcriptionally downregulated. The Connectivity Map (CMap) analysis screen highlighted drugs that affect global gene expression in a similar manner to these psychiatric disorder treatments, including several other antipsychotic drugs, confirming the utility of this approach. The CMap screen specifically identified metergoline, an ergot alkaloid currently used to treat seasonal affective disorder, as a drug of interest. In mice, metergoline dose-dependently reduced MK-801- or methamphetamine-induced locomotor hyperactivity confirming the potential of metergoline to treat positive symptoms of schizophrenia in an animal model. Metergoline had no effects on prepulse inhibition deficits induced by MK-801 or methamphetamine. Taken together, metergoline appears a promising drug for further studies to be repurposed as a treatment for schizophrenia and possibly other psychiatric disorders.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: