Endocannabinoid system imbalance in the postmortem prefrontal cortex of subjects with schizophrenia
| Autor: | Carolina Muguruza, Stephen P.H. Alexander, J Javier Meana, Benito Morentin, Luis F. Callado |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Cannabinoid receptor Prefrontal Cortex Arachidonic Acids Amidohydrolases Glycerides 03 medical and health sciences 0302 clinical medicine Receptor Cannabinoid CB1 medicine Humans Pharmacology (medical) Prefrontal cortex Pharmacology business.industry Human brain Middle Aged medicine.disease Endocannabinoid system Monoacylglycerol Lipases Pathophysiology 030227 psychiatry Psychiatry and Mental health medicine.anatomical_structure nervous system Schizophrenia Female lipids (amino acids peptides and proteins) Carbamates business Neuroscience psychological phenomena and processes 030217 neurology & neurosurgery Endocannabinoids |
| Zdroj: | Journal of Psychopharmacology. 33:1132-1140 |
| ISSN: | 1461-7285 0269-8811 |
| DOI: | 10.1177/0269881119857205 |
| Popis: | Background: The endocannabinoid system – comprising cannabinoid receptors, endocannabinoid ligands and their synthesis and inactivation enzymes – has been widely implicated in the pathophysiology of schizophrenia. However, little is known regarding the status of the different elements of the endocannabinoid system in the brain of schizophrenic patients. We have previously reported altered endocannabinoid levels in the postmortem brain of subjects with schizophrenia compared with matched controls. Aims: Our aim was to further examine the status of the main elements of the endocannabinoid system in the postmortem prefrontal cortex of the same cohort of subjects. Methods: Gene expression and function of the cannabinoid receptor type-1 (CB1) and the endocannabinoid degrading enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have been assessed. Results: A significant decrease in CB1 mRNA levels in schizophrenia was found, without alteration of FAAH or MAGL mRNA expression. Moreover, positive correlations among mRNA expressions of the three genes studied were found in the prefrontal cortex of controls but not in schizophrenic subjects. No alteration was found in CB1 receptor mediated functional coupling to G-proteins, but a significant increase of FAAH activity was found in schizophrenic subjects compared with controls. 2-arachidonoylglycerol levels and MAGL activity were found to positively correlate in controls but not in schizophrenic subjects. Conclusions: The present findings reveal an imbalance in the expression and function of different elements of the endocannabinoid system in schizophrenia. This outcome highlights the relevance of the endocannabinoid system in the pathophysiology of schizophrenia and emphasises its elements as potential targets in the search for new therapeutic strategies. |
| Databáze: | OpenAIRE |
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