PMID- 25080404
OWN - NLM
STAT- MEDLINE
DCOM- 20150703
LR  - 20151119
IS  - 1873-3360 (Electronic)
IS  - 0306-4530 (Linking)
VI  - 49
DP  - 2014 Nov
TI  - Dietary supplementation of omega-3 fatty acids rescues fragile X phenotypes in 
      Fmr1-Ko mice.
PG  - 119-29
LID - S0306-4530(14)00253-4 [pii]
LID - 10.1016/j.psyneuen.2014.07.002 [doi]
AB  - 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.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Pietropaolo, Susanna
AU  - Pietropaolo S
AD  - Institut de Neurosciences Cognitives et Integratives d'Aquitaine (INCIA), CNRS 
      UMR 5287, Bat B2 - Avenue des Facultes, 33405 Talence Cedex, France; Universite 
      de Bordeaux, Bat B2 - Avenue des Facultes, 33405 Talence Cedex, France. 
      Electronic address: susanna.pietropaolo@u-bordeaux.fr.
FAU - Goubran, Mina G
AU  - Goubran MG
AD  - Institut de Neurosciences Cognitives et Integratives d'Aquitaine (INCIA), CNRS 
      UMR 5287, Bat B2 - Avenue des Facultes, 33405 Talence Cedex, France; Universite 
      de Bordeaux, Bat B2 - Avenue des Facultes, 33405 Talence Cedex, France.
FAU - Joffre, Corinne
AU  - Joffre C
AD  - Universite de Bordeaux, Bat B2 - Avenue des Facultes, 33405 Talence Cedex, 
      France; Laboratoire NutriNeurO, UMR INRA 1286, Batiment UFR Pharmacie 2eme 
      Tranche, 146 rue Leo Saignat, 33076 Bordeaux Cedex, France.
FAU - Aubert, Agnes
AU  - Aubert A
AD  - Universite de Bordeaux, Bat B2 - Avenue des Facultes, 33405 Talence Cedex, 
      France; Laboratoire NutriNeurO, UMR INRA 1286, Batiment UFR Pharmacie 2eme 
      Tranche, 146 rue Leo Saignat, 33076 Bordeaux Cedex, France.
FAU - Lemaire-Mayo, Valerie
AU  - Lemaire-Mayo V
AD  - Institut de Neurosciences Cognitives et Integratives d'Aquitaine (INCIA), CNRS 
      UMR 5287, Bat B2 - Avenue des Facultes, 33405 Talence Cedex, France; Universite 
      de Bordeaux, Bat B2 - Avenue des Facultes, 33405 Talence Cedex, France.
FAU - Crusio, Wim E
AU  - Crusio WE
AD  - Institut de Neurosciences Cognitives et Integratives d'Aquitaine (INCIA), CNRS 
      UMR 5287, Bat B2 - Avenue des Facultes, 33405 Talence Cedex, France; Universite 
      de Bordeaux, Bat B2 - Avenue des Facultes, 33405 Talence Cedex, France.
FAU - Laye, Sophie
AU  - Laye S
AD  - Universite de Bordeaux, Bat B2 - Avenue des Facultes, 33405 Talence Cedex, 
      France; Laboratoire NutriNeurO, UMR INRA 1286, Batiment UFR Pharmacie 2eme 
      Tranche, 146 rue Leo Saignat, 33076 Bordeaux Cedex, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140709
PL  - England
TA  - Psychoneuroendocrinology
JT  - Psychoneuroendocrinology
JID - 7612148
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cytokines)
RN  - 0 (Fatty Acids, Omega-3)
RN  - 0 (Fmr1 protein, mouse)
RN  - 0 (Leptin)
RN  - 139135-51-6 (Fragile X Mental Retardation Protein)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Body Composition/drug effects/genetics
MH  - Body Weight/drug effects/genetics
MH  - Brain/*metabolism
MH  - Brain-Derived Neurotrophic Factor/biosynthesis
MH  - Cytokines/*biosynthesis
MH  - Dietary Supplements
MH  - Disease Models, Animal
MH  - Eating/drug effects/genetics
MH  - Fatty Acids, Omega-3/administration & dosage/*therapeutic use
MH  - Female
MH  - Fragile X Mental Retardation Protein/*genetics
MH  - Fragile X Syndrome/*diet therapy/genetics
MH  - Leptin/blood
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Phenotype
OTO - NOTNLM
OT  - Autism
OT  - Cytokines
OT  - Dietary enrichment
OT  - Fragile X
OT  - Gene-environment interactions
OT  - Neurotrophins
EDAT- 2014/08/01 06:00
MHDA- 2015/07/04 06:00
CRDT- 2014/08/01 06:00
PHST- 2014/04/30 00:00 [received]
PHST- 2014/06/13 00:00 [revised]
PHST- 2014/07/01 00:00 [accepted]
PHST- 2014/08/01 06:00 [entrez]
PHST- 2014/08/01 06:00 [pubmed]
PHST- 2015/07/04 06:00 [medline]
AID - S0306-4530(14)00253-4 [pii]
AID - 10.1016/j.psyneuen.2014.07.002 [doi]
PST - ppublish
SO  - Psychoneuroendocrinology. 2014 Nov;49:119-29. doi: 
      10.1016/j.psyneuen.2014.07.002. Epub 2014 Jul 9.