title: Dietary supplementation of omega-3 fatty acids rescues fragile X phenotypes in Fmr1-Ko mice.
abstract: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are known to critically influence brain development and functions. Dietary supplementation with n-3 PUFAs has been suggested as a non-pharmacological therapy for a number of developmental disorders, e.g., autistic spectrum disorders (ASD), but human studies so far have led to conflicting results. Furthermore, it has been hypothesized that the therapeutic impact of n-3 PUFAs on these disorders might be explained by their anti-inflammatory properties and their promoting effects on synaptic function and plasticity, but no clear evidence has been produced in this direction. We evaluated the impact of n-3 PUFA dietary supplementation in a mouse model of fragile X syndrome (FXS), i.e., a major developmental disease and the most frequent monogenic cause of ASD. Fmr1-KO and wild-type mice were provided with a diet enriched or not with n-3 PUFAs from weaning until adulthood when they were tested for multiple FXS-like behaviors. The brain expression of several cytokines and of brain-derived neurotrophic factor (BDNF) was concomitantly assessed as inflammatory and synaptic markers. n-3 PUFA supplementation rescued most of the behavioral abnormalities displayed by Fmr1-KO mice, including alterations in emotionality, social interaction and non-spatial memory, although not their deficits in social recognition and spatial memory. n-3 PUFAs also rescued most of the neuroinflammatory imbalances of KOs, but had a limited impact on their BDNF deficits. These results demonstrate that n-3 PUFAs dietary supplementation, although not a panacea, has a considerable therapeutic value for FXS and potentially for ASD, suggesting a major mediating role of neuroinflammatory mechanisms.
authors: Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), CNRS UMR 5287, Bat B2 - Avenue des Facultés, 33405 Talence Cedex, France; Université de Bordeaux, Bat B2 - Avenue des Facultés, 33405 Talence Cedex, France. Electronic address: susanna.pietropaolo@u-bordeaux.fr.
authors: Susanna
authors: S
authors: Pietropaolo
authors: Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), CNRS UMR 5287, Bat B2 - Avenue des Facultés, 33405 Talence Cedex, France; Université de Bordeaux, Bat B2 - Avenue des Facultés, 33405 Talence Cedex, France.
authors: Mina G
authors: MG
authors: Goubran
authors: Université de Bordeaux, Bat B2 - Avenue des Facultés, 33405 Talence Cedex, France; Laboratoire NutriNeurO, UMR INRA 1286, Bâtiment UFR Pharmacie 2ème Tranche, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
authors: Corinne
authors: C
authors: Joffre
authors: Université de Bordeaux, Bat B2 - Avenue des Facultés, 33405 Talence Cedex, France; Laboratoire NutriNeurO, UMR INRA 1286, Bâtiment UFR Pharmacie 2ème Tranche, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
authors: Agnes
authors: A
authors: Aubert
authors: Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), CNRS UMR 5287, Bat B2 - Avenue des Facultés, 33405 Talence Cedex, France; Université de Bordeaux, Bat B2 - Avenue des Facultés, 33405 Talence Cedex, France.
authors: Valerie
authors: V
authors: Lemaire-Mayo
authors: Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), CNRS UMR 5287, Bat B2 - Avenue des Facultés, 33405 Talence Cedex, France; Université de Bordeaux, Bat B2 - Avenue des Facultés, 33405 Talence Cedex, France.
authors: Wim E
authors: WE
authors: Crusio
authors: Université de Bordeaux, Bat B2 - Avenue des Facultés, 33405 Talence Cedex, France; Laboratoire NutriNeurO, UMR INRA 1286, Bâtiment UFR Pharmacie 2ème Tranche, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
authors: Sophie
authors: S
authors: Layé
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects / Q000235:genetics; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects / Q000235:genetics; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000178:diet therapy* / Q000235:genetics; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D015525:Fatty Acids, Omega-3; D051860:Fragile X Messenger Ribonucleoprotein 1; D020738:Leptin; C497684:Fmr1 protein, mouse
keywords: Autism; Cytokines; Dietary enrichment; Fragile X; Gene–environment interactions; Neurotrophins