Nutritional Omega-3 deficiency abolishes endocannabinoid mediated neuronal functions

Mathieu Lafourcade (1) , Thomas Larrieu (2) , Susana Mato (2) , Anais Duffaud (2) , Marja Sepers (2) , Isabelle Matias (2) , Veronique de Smedt (2) , Virginie Labrousse (2) , Lionel Brétillon (2) , Carlos Matute (2) , Raphael Rodriguez-Puertas (2) , Sophie Layé (2) , Olivier Jacques Manzoni (2)

1 PsyNuGen - Unité de Psychoneuroimmunologie, Nutrition et Génétique
2 Physiopathology of synaptic plasticity

The corollaries of the obesity epidemic that plagues developed societies are malnutrition and resulting biochemical imbalances. Low levels of essential n-3 polyunsaturated fatty acids (n-3 PUFAs) have been linked to neuropsychiatric diseases, but the underlying synaptic alterations are mostly unknown. We found that lifelong n-3 PUFAs dietary insufficiency specifically ablates long-term synaptic depression mediated by endocannabinoids in the prelimbic prefrontal cortex and accumbens. In n-3 deficient mice, presynaptic cannabinoid CB1 receptors (CB1Rs) normally responding to endocannabinoids were uncoupled from their effector Gi/o-proteins. Finally, the dietary-induced reduction of CB1R functions in mood controlling structures is associated with impaired emotional behavior. These findings identify a plausible synaptic substrate for the behavioral alterations caused by the n-3 PUFAs deficiency often observed in western diets

Mots clés: Plasticity; Behaviour; Psychiatric Disorders; Receptors

Domaines: Ingénierie des aliments; Génie des procédés

Mathieu Lafourcade, Thomas Larrieu, Susana Mato, Anais Duffaud, Marja Sepers, et al.. Nutritional Omega-3 deficiency abolishes endocannabinoid mediated neuronal functions. Nature Neuroscience, 2011, 14 (3), pp.345-350. ⟨10.1038/nn.2736⟩. ⟨hal-00612705⟩