Alterations in Gene and Protein Expression of Cannabinoid CB 2 and GPR55 Receptors in the Dorsolateral Prefrontal Cortex of Suicide Victims
María S García-Gutiérrez, Francisco Navarrete, Gemma Navarro, Irene Reyes-Resina, Rafael Franco, Jose Luis Lanciego, Salvador Giner, Jorge Manzanares
Recent studies point to the cannabinoid CB2 receptors (CB2r) and the non-cannabinoid receptor GPR55 as potential key targets involved in the response to stress, anxiety, and depression. Considering the close relationship between neuropsychiatric disorders and suicide, the purpose of this study was to evaluate the potential alterations of CB2r and GPR55 in suicide victims. We analyzed gene and protein expression of both receptors by real-time PCR and western blot, respectively, in the dorsolateral prefrontal cortex (DLPFC) of 18 suicide victims with no clinical psychiatric history or treatment with anxiolytics or antidepressants, and 15 corresponding controls.
We used in situ proximity ligation assay to evaluate whether the receptors formed heteromeric complexes and to determine the expression level of these heteromers, also assessing the co-expression of heteromers in neurons, astroglia, or microglia cells. CB2r and GPR55 gene expressions were significantly lower (by 33 and 41%, respectively) in the DLPFC of suicide cases. CB2r protein expression was higher, as were CB2-GPR55 heteroreceptor complexes.
The results also revealed the presence of CB2-GPR55 receptor heteromers in both neurons and astrocytes, whereas microglial cells showed no expression. We did not observe any significant alterations of GPR55 protein expression. Additional studies will be necessary to evaluate if these alterations are reproducible in suicide victims diagnosed with different psychiatric disorders. Taken together, the results suggest that CB2r and GPR55 may play a relevant role in the neurobiology of suicide.
CITATION Neurotherapeutics. 2018 Jul;15(3):796-806. doi: 10.1007/s13311-018-0610-y.