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Crosstalk between the transcriptional regulation of dopamine D2 and cannabinoid CB1 receptors in schizophrenia: Analyses in patients and in perinatal Delta 9-tetrahydrocannabinol-exposed rats

Identifikátory výsledku

  • Kód výsledku v IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F21%3A43920589" target="_blank" >RIV/00023752:_____/21:43920589 - isvavai.cz</a>

  • Výsledek na webu

    <a href="https://www.sciencedirect.com/science/article/pii/S1043661820316650?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S1043661820316650?via%3Dihub</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.phrs.2020.105357" target="_blank" >10.1016/j.phrs.2020.105357</a>

Alternativní jazyky

  • Jazyk výsledku

    angličtina

  • Název v původním jazyce

    Crosstalk between the transcriptional regulation of dopamine D2 and cannabinoid CB1 receptors in schizophrenia: Analyses in patients and in perinatal Delta 9-tetrahydrocannabinol-exposed rats

  • Popis výsledku v původním jazyce

    Perinatal exposure to Delta(9)-tetrahydrocannabinol (THC) affects brain development and might increase the incidence of psychopathology later in life, which seems to be related to a dysregulation of endocannabinoid and/or dopaminergic systems. We here evaluated the transcriptional regulation of the genes encoding for the cannabinoid CB1 receptor (Cnr1) and the dopamine D2 receptor (Drd2) in perinatal THC-(pTHC) exposed male rats, focusing on the role of DNA methylation analyzed by pyrosequencing. Simultaneously, the molecular and behavioral abnormalities at two different time points (i.e., neonatal age and adulthood) and the potential preventive effect of peripubertal treatment with cannabidiol, a non-euphoric component of Cannabis, were assessed. The DRD2 methylation was also evaluated in a cohort of subjects with schizophrenia. We observed an increase in both Cnr1 and Drd2 mRNA levels selectively in the prefrontal cortex of adult pTHC-exposed rats with a consistent reduction in DNA methylation at the Drd2 regulatory region, paralleled by social withdrawal and cognitive impairment which were reversed by cannabidiol treatment. These adult abnormalities were preceded at neonatal age by delayed appearance of neonatal reflexes, higher Drd2 mRNA and lower 2-arachidonoylglycerol (2-AG) brain levels, which persisted till adulthood. Alterations of the epigenetic mark for DRD2 were also found in subjects with schizophrenia. Overall, reported data add further evidence to the dopamine-cannabinoid interaction in terms of DRD2 and CNR1 dysregulation which could be implicated in the pathogenesis of schizophrenia spectrum disorders, suggesting that cannabidiol treatment may normalize pTHC-induced psychopathology by modulating the altered dopaminergic activity.

  • Název v anglickém jazyce

    Crosstalk between the transcriptional regulation of dopamine D2 and cannabinoid CB1 receptors in schizophrenia: Analyses in patients and in perinatal Delta 9-tetrahydrocannabinol-exposed rats

  • Popis výsledku anglicky

    Perinatal exposure to Delta(9)-tetrahydrocannabinol (THC) affects brain development and might increase the incidence of psychopathology later in life, which seems to be related to a dysregulation of endocannabinoid and/or dopaminergic systems. We here evaluated the transcriptional regulation of the genes encoding for the cannabinoid CB1 receptor (Cnr1) and the dopamine D2 receptor (Drd2) in perinatal THC-(pTHC) exposed male rats, focusing on the role of DNA methylation analyzed by pyrosequencing. Simultaneously, the molecular and behavioral abnormalities at two different time points (i.e., neonatal age and adulthood) and the potential preventive effect of peripubertal treatment with cannabidiol, a non-euphoric component of Cannabis, were assessed. The DRD2 methylation was also evaluated in a cohort of subjects with schizophrenia. We observed an increase in both Cnr1 and Drd2 mRNA levels selectively in the prefrontal cortex of adult pTHC-exposed rats with a consistent reduction in DNA methylation at the Drd2 regulatory region, paralleled by social withdrawal and cognitive impairment which were reversed by cannabidiol treatment. These adult abnormalities were preceded at neonatal age by delayed appearance of neonatal reflexes, higher Drd2 mRNA and lower 2-arachidonoylglycerol (2-AG) brain levels, which persisted till adulthood. Alterations of the epigenetic mark for DRD2 were also found in subjects with schizophrenia. Overall, reported data add further evidence to the dopamine-cannabinoid interaction in terms of DRD2 and CNR1 dysregulation which could be implicated in the pathogenesis of schizophrenia spectrum disorders, suggesting that cannabidiol treatment may normalize pTHC-induced psychopathology by modulating the altered dopaminergic activity.

Klasifikace

  • Druh

    J<sub>imp</sub> - Článek v periodiku v databázi Web of Science

  • CEP obor

  • OECD FORD obor

    30104 - Pharmacology and pharmacy

Návaznosti výsledku

  • Projekt

    Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

  • Návaznosti

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Ostatní

  • Rok uplatnění

    2021

  • Kód důvěrnosti údajů

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Údaje specifické pro druh výsledku

  • Název periodika

    Pharmacological Research

  • ISSN

    1043-6618

  • e-ISSN

  • Svazek periodika

    164

  • Číslo periodika v rámci svazku

    "Article Number: 105357"

  • Stát vydavatele periodika

    GB - Spojené království Velké Británie a Severního Irska

  • Počet stran výsledku

    10

  • Strana od-do

    1-10

  • Kód UT WoS článku

    000615153300017

  • EID výsledku v databázi Scopus

    2-s2.0-85099693901