title: Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions.
abstract: 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 CB(1) receptors (CB(1)Rs) normally responding to endocannabinoids were uncoupled from their effector G(i/o) proteins. Finally, the dietary-induced reduction of CB(1)R functions in mood-controlling structures was associated with impaired emotional behavior. These findings identify a plausible synaptic substrate for the behavioral alterations caused by the n-3 PUFAs deficiency that is often observed in western diets.
authors.affiliation: INSERM U862, Physiopathology of Synaptic Plasticity Group, Neurocentre Magendie, Bordeaux Cedex, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lafourcade
authors.forename: Thomas
authors.initials: T
authors.lastname: Larrieu
authors.forename: Susana
authors.initials: S
authors.lastname: Mato
authors.forename: Anais
authors.initials: A
authors.lastname: Duffaud
authors.forename: Marja
authors.initials: M
authors.lastname: Sepers
authors.forename: Isabelle
authors.initials: I
authors.lastname: Matias
authors.forename: Veronique
authors.initials: V
authors.lastname: De Smedt-Peyrusse
authors.forename: Virginie F
authors.initials: VF
authors.lastname: Labrousse
authors.forename: Lionel
authors.initials: L
authors.lastname: Bretillon
authors.forename: Carlos
authors.initials: C
authors.lastname: Matute
authors.forename: Rafael
authors.initials: R
authors.lastname: Rodríguez-Puertas
authors.forename: Sophie
authors.initials: S
authors.lastname: Layé
authors.forename: Olivier J
authors.initials: OJ
authors.lastname: Manzoni
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D004032:Diet; D004644:Emotions / Q000502:physiology; D063388:Endocannabinoids; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005260:Female; D006801:Humans; D044342:Malnutrition / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009714:Nucleus Accumbens / Q000502:physiology; D017397:Prefrontal Cortex / Q000502:physiology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013569:Synapses / Q000502:physiology
chemical_list: D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D015525:Fatty Acids, Omega-3; D043884:Receptor, Cannabinoid, CB1