KAUST Research Workshop on Innovative Technologies to Study Brain Energy Metabolism
NeuroCentre Magendie, Bordeaux, France
Giovanni Marsicano is Group leader of the Team “Endocannabinoids and Neuroadaptation”, INSERM U862 NeuroCentre Magendie, Bordeaux (France). His research is directed towards understanding the molecular basis of behavioural adaptation. In particular, his group is interested in the endocannabinoid system (ECS) which regulates many important brain fonctions such as anxiety, food intake and energy balance.
Brain activity critically depends on the high energetic support provided by mitochondria, the cell organelles transforming energy sources into ATP. The endocannabinoid system controls a large amount of brain and peripheral functions, and cannabinoid treatment alters key brain functions in humans and animals. We recently discovered that the G protein-coupled type-1 cannabinoid receptor (CB1) is functionally located not only at the cellular plasma membrane, but also at brain mitochondrial membranes, where it can directly control mitochondrial energetic activity ("mitochondrial" CB1, mtCB1). Whereas the pathological impact of chronic mitochondrial dysfunctions in the brain is well established, the involvement of ongoing modulation of mitochondrial activity in brain functions is unknown. In this talk, I will introduce specific functions of brain CB1 receptors and show how cannabinoid-induced behavioral alterations require activation of mtCB1 receptors in different brain regions and cell types, including neurons and astrocytes. Thus, the G protein-coupled mtCB1 receptors regulate behavioral processes via modulation of mitochondrial energy metabolism. By directly linking mitochondrial activity to high brain functions, these studies reveal that (endo)cannabinoid signaling exerts several of its main functions by directly modulating brain bioenergetics. Therefore, the study of the functions of mtCB1 receptors represents an innovative tool to better understand the impact of brain energy metabolism on behavior.