Lifelong imbalanced LA/ALA intake impairs emotional and cognitive behavior via changes in brain endocannabinoid system

Erica Zamberletti, Fabiana Piscitelli, Valentina De Castro, Elisabetta Murru, Marina Gabaglio, Paola Colucci, Chiara Fanali, Pamela Prini, Tiziana Bisogno, Mauro Maccarrone, Patrizia Campolongo, Sebastiano Banni, Tiziana Rubino, Daniela Parolaro

Research output: Contribution to journalArticlepeer-review


Imbalanced dietary n-3 and n-6 PUFA content has been associated with a number of neurological conditions. Endocannabinoids are n-6 PUFA derivatives, whose brain concentrations are sensitive to modifications of fatty acid composition of the diet and play a central role in the regulation of mood and cognition. As such, the endocannabinoid system appears to be an ideal candidate for mediating the effects of dietary fatty acids on mood and cognition. Lifelong administration of isocaloric α-linolenic acid (ALA)-deficient and -enriched diets induced short-term memory deficits, whereas only dietary ALA enrichment altered emotional reactivity in adult male rats compared with animals fed a standard diet that was balanced in ALA/linoleic acid (LA) ratio. In the prefrontal cortex, both diets reduced 2-AG levels and increased MAG lipase expression, whereas only the enriched diet reduced AEA levels, simultaneously increasing FAAH expression. In the hippocampus, an ALA-enriched diet decreased AEA content and NAPE-PLD expression, and reduced 2-AG content while increasing MAG lipase expression. These findings highlight the importance of a diet balanced in fatty acid content for normal brain functions and to support a link between dietary ALA, the brain endocannabinoid system, and behavior, which indicates that dietary ALA intake is a sufficient condition for altering the endocannabinoid system in brain regions modulating mood and cognition.

Original languageEnglish
Pages (from-to)301-316
Number of pages16
JournalJournal of Lipid Research
Issue number2
Publication statusE-pub ahead of print - Nov 30 2016


  • Journal Article


Dive into the research topics of 'Lifelong imbalanced LA/ALA intake impairs emotional and cognitive behavior via changes in brain endocannabinoid system'. Together they form a unique fingerprint.

Cite this