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Transcriptional Effects of Psychoactive Drugs on Genes Involved in Neurogenesis.

ABSTRACT: 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.

SUBMITTER: Bortolasci CC

PROVIDER: S-EPMC7672551 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Transcriptional Effects of Psychoactive Drugs on Genes Involved in Neurogenesis.

Bortolasci Chiara C CC Spolding Briana B Kidnapillai Srisaiyini S Connor Timothy T Truong Trang T T TTT Liu Zoe S J ZSJ Panizzutti Bruna B Richardson Mark F MF Gray Laura L Berk Michael M Dean Olivia M OM Walder Ken K

International journal of molecular sciences 20201106 21

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. ...[more]

PMID: 33172123

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Project description:BackgroundThe misuse of illicit substances is associated with increased morbidity and mortality; thus, substance abuse is a global health concern. The Arabian Gulf region is considered a crossing point and a consumer of illicit drugs. However, a lack of laboratory-based research has limited the scientific assessment of drug misuse in the Arabian Gulf region. Thus, an up-to-date analytical representation of the drug situation is warranted.MethodsWe investigated the type and quantity of detained narcotic drugs and psychotropic substances from 2015 to 2018, representing a population of approximately 4 million people, in addition to the number of abusers and mortality among abusers. In total, 6220 cases from the Narcotic and Psychotropic Laboratory and 17,755 cases from the Forensic Toxicology Laboratory were reviewed and analyzed. Substances were identified and documented using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry.ResultsCannabis, including marijuana, was the most seized substance, followed by heroin, opium, and cocaine. Amphetamines, including methamphetamine, in the form of powder or pills, were seized in larger quantities than other psychoactive substances. The most consumed substances were, in order, amphetamines (including methamphetamine), benzodiazepines, cannabis, and heroin. We identify the common drugs in postmortem specimens, according to sex, from suspected drug-related deaths. The most common single drug identified were heroin, benzodiazepines, and methamphetamine. Similarly, the multiple-drug cocktail of heroin-benzodiazepines, cannabis-benzodiazepines, and cannabis-amphetamines, were detected frequently.ConclusionsThe data shows that cannabis is the leading type of illicit substance seized. Deaths resulting from benzodiazepines and heroin abuse were the highest in the single drug category, while heroin-benzodiazepines combination deaths were the highest in the multiple-drug category. Methamphetamine was the most abused illicit drug in Kuwait. These findings revealed the illicit drug abuse situation in the State of Kuwait, in a region that suffers from the scarcity of information regarding illicit substances. Thus, providing valuable information for drug enforcement, forensic analyst, health workers on national and international levels.

Project description:BACKGROUND: Success of meat production and selection for improvement of meat quality is among the primary aims in animal production. Meat quality traits are economically important in swine; however, the underlying genetic nature is very complex. Therefore, an improved pork production strongly depends on identifying and studying how genetic variations contribute to modulate gene expression. Promoters are key regions in gene modulation as they harbour several binding motifs to transcription regulatory factors. Therefore, polymorphisms in these regions are likely to deeply affect RNA levels and consequently protein synthesis. In this study, we report the identification of single nucleotide polymorphisms (SNPs) in promoter regions of candidate genes involved in development, cellular differentiation and muscle growth in Sus scrofa. We identified SNPs in the promoter regions of genes belonging to the Myogenic Regulatory Factors (MRF) gene family (the Myogenic Differentiation gene, MYOD1) and to Growth and Differentiation Factors (GDF) gene family (Myostatin gene, MSTN, GDF8), in Casertana and Large White breeds. The purpose of this study was to investigate if polymorphisms in the promoters could affect the transcriptional activity of these genes. With this aim, we evaluated in vitro the functional activity of the luciferase reporter gene luc2 activity, driven by two constructs carrying different promoter haplotypes. RESULTS: We tested the effects of the G302A (U12574) transition on the promoter efficiency in MYOD1 gene. We ascertained a difference in transcription efficiency for the two variants. A stronger activity of the A-carrying construct is more evident in C2C12. The luciferase expression driven by the MYOD1-A allelic variant displayed a 3.8-fold increased transcriptional activity. We investigated the activity of two haplotype variants (AY527152) in the promoter of GDF8 gene. The haploptype-1 (A435-A447-A879) up-regulated the expression of the reporter gene by a two-fold increase, and hence presumably of the GDF8 gene, in both CHO and C2C12 cultured cells. CONCLUSIONS: In vitro the MYOD1-A allelic variant could up-regulate the expression of MYOD1 gene. Additionally, we could assess a different response of in vitro gene expression according to cell type used to transfect constructs, suggesting that MyoD activation is regulated by mechanisms that are specific of myoblasts.

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Transcriptional Effects of Psychoactive Drugs on Genes Involved in Neurogenesis.

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Transcriptional Effects of Psychoactive Drugs on Genes Involved in Neurogenesis.

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