A preliminary study of endocannabinoid system regulation in psychosis: Distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem
PubMed
28108228
DOI
10.1016/j.schres.2017.01.022
PII: S0920-9964(17)30031-2
Knihovny.cz E-zdroje
- Klíčová slova
- Cannabinoid receptor type-1, DNA methylation, Endocannabinoid system (ECS), Methylazoxymethanol (MAM) rat model, Schizophrenia,
- MeSH
- bipolární porucha genetika metabolismus MeSH
- CpG ostrůvky MeSH
- depresivní porucha unipolární genetika metabolismus MeSH
- endokanabinoidy metabolismus MeSH
- kohortové studie MeSH
- leukocyty mononukleární metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- methylazoxymethanolacetát MeSH
- metylace DNA * MeSH
- modely nemocí na zvířatech MeSH
- potkani Sprague-Dawley MeSH
- prefrontální mozková kůra metabolismus MeSH
- promotorové oblasti (genetika) * MeSH
- receptor kanabinoidní CB1 genetika metabolismus MeSH
- regulace genové exprese MeSH
- schizofrenie genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- CNR1 protein, human MeSH Prohlížeč
- Cnr1 protein, rat MeSH Prohlížeč
- endokanabinoidy MeSH
- methylazoxymethanolacetát MeSH
- receptor kanabinoidní CB1 MeSH
Compelling evidence supports the involvement of the endocannabinoid system (ECS) in psychosis vulnerability. We here evaluated the transcriptional regulation of ECS components in human peripheral blood mononuclear cells (PBMCs) obtained from subjects suffering from bipolar disorder, major depressive disorder and schizophrenia, focusing in particular on the effects of DNA methylation. We observed selective alterations of DNA methylation at the promoter of CNR1, the gene coding for the type-1 cannabinoid receptor, in schizophrenic patients (N=25) with no changes in any other disorder. We confirmed the regulation of CNR1 in a well-validated animal model of schizophrenia, induced by prenatal methylazoxymethanol (MAM) acetate exposure (N=7 per group) where we found, in the prefrontal cortex, a significant increase in CNR1 expression and a consistent reduction in DNA methylation at specific CpG sites of gene promoter. Overall, our findings suggest a selective dysregulation of ECS in psychosis, and highlight the evaluation of CNR1 DNA methylation levels in PBMCs as a potential biomarker for schizophrenia.
CEITEC Masaryk University Brno Czech Republic
Faculty of Bioscience and Technology for Food Agriculture and Environment University of Teramo Italy
Masaryk University Faculty of Medicine Department of Pharmacology Brno Czech Republic
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