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Effects of Psychotropic Drugs on Ribosomal Genes and Protein Synthesis
journal contribution
posted on 2022-10-28, 00:30 authored by Zoe LiuZoe Liu, Thi Thuy Trang TruongThi Thuy Trang Truong, Chiara BortolasciChiara Bortolasci, Briana RandallBriana Randall, B Panizzutti, Courtney SwintonCourtney Swinton, Jee Hyun KimJee Hyun Kim, S Kidnapillai, Mark RichardsonMark Richardson, Laura GrayLaura Gray, Olivia DeanOlivia Dean, Sean McgeeSean Mcgee, M Berk, Ken WalderKen WalderAltered protein synthesis has been implicated in the pathophysiology of several neuropsychiatric disorders, particularly schizophrenia. Ribosomes are the machinery responsible for protein synthesis. However, there remains little information on whether current psychotropic drugs affect ribosomes and contribute to their therapeutic effects. We treated human neuronal-like (NT2-N) cells 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), valproate (0.5 mM) or vehicle control for 24 h. Transcriptomic and gene set enrichment analysis (GSEA) identified that the ribosomal pathway was altered by these drugs. We found that three of the eight drugs tested significantly decreased ribosomal gene expression, whilst one increased it. Most changes were observed in the components of cytosolic ribosomes and not mitochondrial ribosomes. Protein synthesis assays revealed that aripiprazole, clozapine and lithium all decreased protein synthesis. Several currently prescribed psychotropic drugs seem to impact ribosomal gene expression and protein synthesis. This suggests the possibility of using protein synthesis inhibitors as novel therapeutic agents for neuropsychiatric disorders.
History
Journal
International Journal of Molecular SciencesVolume
23Publisher DOI
ISSN
1661-6596eISSN
1422-0067Usage metrics
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Categories
Keywords
Science & TechnologyLife Sciences & BiomedicinePhysical SciencesBiochemistry & Molecular BiologyChemistry, MultidisciplinaryChemistryribosomeprotein translationpsychotropic druggene expressionschizophreniabipolar disorderpsychiatryneurosciencemental disordersOXIDATIVE STRESSEXPRESSIONCLOZAPINEMUTATIONSCELLSTRANSCRIPTOMEARIPIPRAZOLEHYPOGLYCEMIA