A preliminary study of endocannabinoid system regulation in psychosis: Distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia
Language English Country Netherlands Media print-electronic
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
28108228
DOI
10.1016/j.schres.2017.01.022
PII: S0920-9964(17)30031-2
Knihovny.cz E-resources
- Keywords
- Cannabinoid receptor type-1, DNA methylation, Endocannabinoid system (ECS), Methylazoxymethanol (MAM) rat model, Schizophrenia,
- MeSH
- Bipolar Disorder genetics metabolism MeSH
- CpG Islands MeSH
- Depressive Disorder, Major genetics metabolism MeSH
- Endocannabinoids metabolism MeSH
- Cohort Studies MeSH
- Leukocytes, Mononuclear metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Methylazoxymethanol Acetate MeSH
- DNA Methylation * MeSH
- Disease Models, Animal MeSH
- Rats, Sprague-Dawley MeSH
- Prefrontal Cortex metabolism MeSH
- Promoter Regions, Genetic * MeSH
- Receptor, Cannabinoid, CB1 genetics metabolism MeSH
- Gene Expression Regulation MeSH
- Schizophrenia genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- CNR1 protein, human MeSH Browser
- Cnr1 protein, rat MeSH Browser
- Endocannabinoids MeSH
- Methylazoxymethanol Acetate MeSH
- Receptor, Cannabinoid, 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
References provided by Crossref.org
The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology
