Dietary supplementation of omega-3 fatty acids rescues fragile X phenotypes in Fmr1-Ko mice.
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.
['Pietropaolo|Susanna|S|', 'Goubran|Mina G|MG|', 'Joffre|Corinne|C|', 'Aubert|Agnes|A|', 'Lemaire-Mayo|Valerie|V|', 'Crusio|Wim E|WE|', 'Layé|Sophie|S|']
D000818:Animals D015415:Biomarkers D001823:Body Composition D001835:Body Weight D001921:Brain D019208:Brain-Derived Neurotrophic Factor D016207:Cytokines D019587:Dietary Supplements D004195:Disease Models, Animal D004435:Eating D015525:Fatty Acids, Omega-3 D005260:Female D051860:Fragile X Mental Retardation Protein D005600:Fragile X Syndrome D020738:Leptin D008297:Male D051379:Mice D018345:Mice, Knockout D010641:Phenotype
Fragile X Cytokines Autism Dietary enrichment Gene–environment interactions Neurotrophins