Dietary supplementation of omega-3 fatty acids rescues fragile X phenotypes in Fmr1 -Ko mice

• Published in: Psychoneuroendocrinology 2014-11, Vol.49, p.119-129
• Main Authors: Pietropaolo, Susanna, Goubran, Mena, Joffre, Corinne, Aubert, Agnes, Lemaire-Mayo, Valerie, Crusio, Wim E, Layé, Sophie
• Format: Article
• Language: English
• Subjects: Animals; Autism; Behavioral psychophysiology; Biological and medical sciences; Biomarkers - metabolism; Body Composition - drug effects; Body Composition - genetics; Body Weight - drug effects; Body Weight - genetics; Brain - metabolism; Brain-Derived Neurotrophic Factor - biosynthesis; Child clinical studies; Chromosome fragility (bloom syndrome, ataxia telangiectasia, fanconi anemia, x-linked mental retardation...); Cytokines; Cytokines - biosynthesis; Developmental disorders; Dietary enrichment; Dietary Supplements; Disease Models, Animal; Eating - drug effects; Eating - genetics; Endocrinology & Metabolism; Fatty Acids, Omega-3 - administration & dosage; Fatty Acids, Omega-3 - therapeutic use; Female; Fragile X; Fragile X Mental Retardation Protein - genetics; Fragile X Syndrome - diet therapy; Fragile X Syndrome - genetics; Fundamental and applied biological sciences. Psychology; Gene–environment interactions; Hormones and behavior; Infantile autism; Leptin - blood; Life Sciences; Male; Medical genetics; Medical sciences; Mice; Mice, Knockout; Neurotrophins; Phenotype; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry
• ISSN: 0306-4530; 1873-3360
• DOI: 10.1016/j.psyneuen.2014.07.002

Summary 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.