title: Lifelong imbalanced LA/ALA intake impairs emotional and cognitive behavior via changes in brain endocannabinoid system.
abstract: 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.
authors.affiliation: Department of Biotechnology and Life Sciences (DBSV), University of Insubria, Busto Arsizio (VA), Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Zamberletti
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Piscitelli
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: De Castro
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Murru
authors.affiliation: Department of Biotechnology and Life Sciences (DBSV), University of Insubria, Busto Arsizio (VA), Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Gabaglio
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Colucci
authors.affiliation: Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fanali
authors.affiliation: Department of Biotechnology and Life Sciences (DBSV), University of Insubria, Busto Arsizio (VA), Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Prini
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy.|Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bisogno
authors.affiliation: Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy.|European Center for Brain Research/IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Campolongo
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Banni
authors.affiliation: Department of Biotechnology and Life Sciences (DBSV), University of Insubria, Busto Arsizio (VA), Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Rubino
authors.affiliation: Department of Biotechnology and Life Sciences (DBSV), University of Insubria, Busto Arsizio (VA), Italy daniela.parolaro@uninsubria.it.|Zardi Gori Foundation, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Parolaro
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism; D004644:Emotions / Q000187:drug effects / Q000502:physiology*; D063388:Endocannabinoids / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D019787:Linoleic Acid / Q000008:administration & dosage / Q000378:metabolism; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017962:alpha-Linolenic Acid / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D063388:Endocannabinoids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D017962:alpha-Linolenic Acid; D019787:Linoleic Acid
keywords: cognition; diet; linoleic acid; mood; α-linolenic acid