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

Psychoneuroendocrinology. 2014 Nov;49:119-29. doi: 10.1016/j.psyneuen.2014.07.002. Epub 2014 Jul 9.

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.

Keywords: Autism; Cytokines; Dietary enrichment; Fragile X; Gene–environment interactions; Neurotrophins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Body Composition / drug effects
  • Body Composition / genetics
  • Body Weight / drug effects
  • Body Weight / genetics
  • Brain / metabolism*
  • Brain-Derived Neurotrophic Factor / biosynthesis
  • Cytokines / biosynthesis*
  • Dietary Supplements
  • Disease Models, Animal
  • Eating / drug effects
  • Eating / genetics
  • Fatty Acids, Omega-3 / administration & dosage
  • Fatty Acids, Omega-3 / therapeutic use*
  • Female
  • Fragile X Mental Retardation Protein / genetics*
  • Fragile X Syndrome / diet therapy*
  • Fragile X Syndrome / genetics
  • Leptin / blood
  • Male
  • Mice
  • Mice, Knockout
  • Phenotype

Substances

  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • Cytokines
  • Fatty Acids, Omega-3
  • Fmr1 protein, mouse
  • Leptin
  • Fragile X Mental Retardation Protein