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Cannabinoid CB1 receptor signaling in the brain: the where matters| old_uid | 11987 |
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| title | Cannabinoid CB1 receptor signaling in the brain: the where matters |
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| start_date | 2013/01/14 |
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| schedule | 11h |
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| online | no |
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| details | Invité par Alberto Bacci |
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| summary | The endocannabinoid system in the brain is formed mainly by type-1 cannabinoid receptors (CB1), their endogenous lipid ligands (endocannabinoids) and by the enzymatic machineries for endocannabinoid synthesis and degradation. CB1 receptors are probably the most abundant G Protein Coupled Receptor expressed in the brain. Indeed, they are present in different brain regions and, most importantly, in different cell types. Moreover, at subcellular level, recent data indicate that CB1 is present not only at plasma membranes, but also in intracellular compartments, where it is still able to be activated by lipid cell-permeable ligands. For instance, CB1 receptors are abundantly expressed at terminals of inhibitory GABAergic neurons, where they negatively control the release of GABA. However, CB1 receptors are also expressed, though at much lower levels, in cortical glutamatergic neurons, where they also negatively control glutamate release. Moreover, recent data indicate that even lower, but functionally important, levels of CB1 receptors are expressed in brain astroglial cells, where they might participate in astroglial-neuronal interactions at synaptic level. Finally, our recent work revealed that CB1 receptors are localized at mitochondria membranes in the brain, where they can directly regulate mitochondrial respiration, single cell metabolism and participate in synaptic plasticity. Our work in the last years focused on the genetic, pharmacological, behavioral and electrophysiological dissection of the cell type- and subcellular-specific localization of CB1 receptors in the brain. In particular, this lecture will summarize recent data showing that the opposite control of GABAergic and glutamatergic transmission by CB1 signaling results in a bimodal control of simple behaviors, such as modulation of food intake. Moreover, the role of astroglial CB1 receptors in short-term memory processes (working memory) will be described. Finally, the novel and surprising roles of CB1 receptors at brain mitochondrial level (mtCB1) will be presented. Altogether, these data represent a demonstration that the functional impact of CB1 receptors in mouse behavior and physiology is not an intrinsic property, but it is an emerging quality of the receptor, depending on the cell type and/or the subcellular compartment where CB1 receptors are present. This idea might be logically extended to any component of the brain and should provide a theoretical and experimental framework to better understand the incomparable complexity of this organ. Moreover, the possible identification of specific emerging pharmacological properties of CB1 receptors present in specific brain cell type or subcellular compartments might pave the way to novel therapeutic approaches to exploit the potentialities of the endocannabinoid system for many brain diseases, possibly avoiding undesired side effects. |
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| responsibles | Miles |
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