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

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

Author information

1
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.
2
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.
3
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.

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

PMID:
25080404
DOI:
10.1016/j.psyneuen.2014.07.002
[Indexed for MEDLINE]

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