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14 (3), 345-50

Mar 2011

Nutritional omega-3 Deficiency Abolishes Endocannabinoid-Mediated Neuronal Functions

Mathieu Lafourcade 1Thomas LarrieuSusana MatoAnais DuffaudMarja SepersIsabelle MatiasVeronique De Smedt-PeyrusseVirginie F LabrousseLionel BretillonCarlos MatuteRafael Rodríguez-PuertasSophie LayéOlivier J Manzoni

PMID: 21278728

DOI:10.1038/nn.2736

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

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