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Edgar Soria-Gomez & Arnau Busquets-Garcia dans Bioessays

Focus sur la modulation du comportement par les récepteurs CB1 : l’importance de son profil d’expression

Le 26 août 2015

Dissecting the cannabinergic control of behavior: The where matters.
Arnau Busquets-Garcia, Tifany Desprez, Mathilde Metna-Laurent, Luigi Bellocchio, Giovanni Marsicano and Edgar Soria-Gomez
Bioessays. 2015 Aug 11. doi: 10.1002/bies.201500046. [Epub ahead of print]

Group "Endocannabinoids and Neuroadaptation," NeuroCentre Magendie, INSERM U862, Bordeaux Neurocampus, University of Bordeaux, Bordeaux, France.


Edgar Soria-Gomez: "The endocannabinoid system (ECS) is an important neuromodulator system. And it is the target of the main psychoactive component of the plant cannabis sativa, the THC. Which exerts its effect by binding cannabinoid receptors, CB1 and CB2. The endogenous ligands of these receptors are a family of lipids called endocannabinoids, like anandamide and 2-AG. The major effect of CB1 activation is the decrease of neuronal excitability and the presynaptic reduction of neurotransmitter release. During the last years our lab and others provided different advanced conditional genetic tools, allowing the deletion of CB1 receptors in specific cell types in mice. These mice become a fantastic tool to explore the specificities that explain the different functions of the ECS.

 Thus, the last years appear numerous works demonstrating in a more specific way how the ECS can modulate different functions. These works clearly demonstrate different effects depending on the cell type where the CB1 receptor is found, which or where the endocannabinoids could act and potential new localizations of the receptors. In order to highlight and discuss all this exciting new findings and open new directions in the endocannabinoid system field we wrote this review that deals with the cell specificity modulation of the endocannabinoid system.Interestingly, we go from the cell type differences inside different brain regions in order to explain the behavioral outputs modulate by the ECS.

In this review we focused on two different functions controlled by the ECS that are memory processes and food intake. These are two example of how this system could control physiological functions in a very specific way. Finally, in this manuscript we also review the new exciting finding about the mitochondrial localization of CB1R. Interestingly, beside the well-known expression of the CB1 receptor in the plasma membrane of different cell types, it can also be found in intracellular compartments, such as in the mitochondria, where it modulates mitochondrial respiration and energy production. Present and future research will determine which are the behavioral outputs regulated by the mitochondrial CB1 receptor.

As you can see in this review, more and more questions are generated in the ECS field and we have to go on with our research to better understand how this system works. Interestingly, the involvement of the endocannabinoid system in a plethora of neurological and neuropsychiatric diseases makes this system a very interesting target for therapeutic approaches. Indeed, one of the big challenges in cannabinoid research is to translate what has been found in animal models to human subjects. Always taking into account that the where matters. Overall, understanding the molecular, cellular, network and behavioral functions of the endocannabinoid system will strongly contribute to our knowledge of brain processes and will suggest innovative therapeutic strategies for brain disorders"

Edgar Soria-Gomez / PhD Neurocentre Magendie 146 rue Léo Saignat 33077 Bordeaux (edgar.soria @ inserm.fr)
Dernière mise à jour le 27.08.2015

Auteurs



Edgar Soria-Gomez
Postdoc, since November 2009 in the team of Giovanni Marsicano.
Defended his PhD thesis in July 2009, in Mexico City, in the “Universidad Nacional Autonoma de Mexico, UNAM"



Arnau Busquets-Garcia
Position: Postdoc since January 2014. Team of Giovanni Marsicano

PhD Thesis defence: July 2013.
University: Pompeau Fabra, Barcelona, Spain.