Dietary supplementation of omega-3 fatty acids rescues fragile X phenotypes in Fmr1-Ko mice
Psychoneuroendocrinology. 2014-11-01; 49: 119-129
DOI: 10.1016/j.psyneuen.2014.07.002
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Pietropaolo S(1), Goubran MG(2), Joffre C(3), Aubert A(3), Lemaire-Mayo V(2), Crusio WE(2), Layé S(3).
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: .
(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.
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.