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A preliminary study of endocannabinoid system regulation in psychosis: Distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia

C. D'Addario, V. Micale, M. Di Bartolomeo, T. Stark, M. Pucci, A. Sulcova, M. Palazzo, Z. Babinska, L. Cremaschi, F. Drago, A. Carlo Altamura, M. Maccarrone, B. Dell'Osso,

. 2017 ; 188 (-) : 132-140. [pub] 20170117

Jazyk angličtina Země Nizozemsko

Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc18025188

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.

Citace poskytuje Crossref.org

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$a Compelling evidence supports the involvement of the endocannabinoid system (ECS) in psychosis vulnerability. We here evaluated the transcriptional regulation of ECS components in human peripheral blood mononuclear cells (PBMCs) obtained from subjects suffering from bipolar disorder, major depressive disorder and schizophrenia, focusing in particular on the effects of DNA methylation. We observed selective alterations of DNA methylation at the promoter of CNR1, the gene coding for the type-1 cannabinoid receptor, in schizophrenic patients (N=25) with no changes in any other disorder. We confirmed the regulation of CNR1 in a well-validated animal model of schizophrenia, induced by prenatal methylazoxymethanol (MAM) acetate exposure (N=7 per group) where we found, in the prefrontal cortex, a significant increase in CNR1 expression and a consistent reduction in DNA methylation at specific CpG sites of gene promoter. Overall, our findings suggest a selective dysregulation of ECS in psychosis, and highlight the evaluation of CNR1 DNA methylation levels in PBMCs as a potential biomarker for schizophrenia.
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$a Micale, Vincenzo $u CEITEC/Masaryk University, Brno, Czech Republic; Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy.
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$a Di Bartolomeo, Martina $u Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Italy.
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$a Babinska, Zuzana $u Masaryk University, Faculty of Medicine, Department of Pharmacology, Brno, Czech Republic.
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$a Cremaschi, Laura $u Department of Neuroscience, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
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