Contribution du récepteur GPR55 à la synaptogenèse
Functional connections between nerve cells (called synapses) are essential to establish the architecture of the nervous system. The modification of synapses is thought to be one of the mechanisms by which learning and memory occur. It has been known for decades that cannabis consumption has a profound influence on learning and memory, and that maternal marijuana smoking during perinatal period causes cognitive deficits that last in the adulthood of the offspring. For the moment, we do not know if these effects are mediated by the classic CB1 and CB2 cannabinoid receptors or by other receptors such as GPR55. Recent studies by Pr. Bouchard have demonstrated an important role for the endocannabinoid system in the development of the nervous system, including the presence of GPR55 and its involvement in axon growth and target innervation during the fetal and early postnatal periods. As certain molecules and cellular mechanisms involved in these processes may also regulate synapse formation (synaptogenesis), the objective of the present study is to determine the contribution of GPR55 in the formation of new synaptic contacts. Primary cortical neurons isolated from embryonic mice were cultivated and then treated either with a selective agonist of GPR55 (O-1602) or his selective antagonist (ML-193), or with a phytocannabinoid (cannabidiol) for 24h at the ninth day in vitro (DIV9). In immunocytochemistry, neurons treated with ML-193 have shown a decrease in synaptic density, while the treatment with O-1602 or cannabidiol increased it. These anatomical changes were correlated with changes in the expression of synaptic proteins GluR1 and synaptophysin. Results from this study provide important insight on the development of the nervous system and contribute to improving our knowledge on developmental abnormalities induced by perinatal cannabis use.
GPR55 Synaptogenesis Cannabinoids Development of the central nervous system