N‐3 PUFA deficiency disrupts oligodendrocyte maturation and myelin integrity during brain development
Quentin Leyrolle
(1)
,
Fanny Decoeur
(1)
,
Cyril Dejean
(2)
,
Marie-Galadriel Briere
(3)
,
Stephane Leon
(1)
,
Ioannis Bakogiannis
(1)
,
Emilie Baroux
(1)
,
Tony‐lee Sterley
(4)
,
Clémentine Bosch-Bouju
(1)
,
Lydie Morel
(1)
,
Camille Amadieu
(1)
,
Cynthia Lecours
(5, 6)
,
Marie‐kim St‐pierre
(5, 6)
,
Maude Bordeleau
(5, 6, 7)
,
Veronique de Smedt-Peyrusse
(1)
,
Alexandra Sere
(1)
,
Leslie Schwendimann
(8)
,
Stéphane Grégoire
(9, 10)
,
Lionel Brétillon
(9, 10)
,
Niyazi Acar
(9, 10)
,
Corinne Joffre
(1)
,
Guillaume Ferreira
(1)
,
Raluca Uricaru
(3)
,
Patricia Thebault
(3)
,
Pierre Gressens
(8)
,
Marie‐eve Tremblay
(5, 6, 7, 11)
,
Sophie Layé
(1)
,
Agnes Nadjar
(1)
1
NutriNeuro -
Nutrition et Neurobiologie intégrée
2 U1215 Inserm - UB - Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale
3 LaBRI - Laboratoire Bordelais de Recherche en Informatique
4 University of Calgary
5 ULaval - Université Laval [Québec]
6 UVIC - University of Victoria [Canada]
7 UQAM - Université du Québec à Montréal = University of Québec in Montréal
8 NeuroDiderot (UMR_S_1141 / U1141) - Maladies neurodéveloppementales et neurovasculaires
9 CSGA - Centre des Sciences du Goût et de l'Alimentation [Dijon]
10 UBFC - Université Bourgogne Franche-Comté [COMUE]
11 UNBC - University of Northern British Columbia [Prince George]
2 U1215 Inserm - UB - Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale
3 LaBRI - Laboratoire Bordelais de Recherche en Informatique
4 University of Calgary
5 ULaval - Université Laval [Québec]
6 UVIC - University of Victoria [Canada]
7 UQAM - Université du Québec à Montréal = University of Québec in Montréal
8 NeuroDiderot (UMR_S_1141 / U1141) - Maladies neurodéveloppementales et neurovasculaires
9 CSGA - Centre des Sciences du Goût et de l'Alimentation [Dijon]
10 UBFC - Université Bourgogne Franche-Comté [COMUE]
11 UNBC - University of Northern British Columbia [Prince George]
Cyril Dejean
- Fonction : Auteur
- PersonId : 1375772
- ORCID : 0000-0002-2592-7502
Clémentine Bosch-Bouju
- Fonction : Auteur
- PersonId : 747607
- IdHAL : clemboschbouju
- ORCID : 0000-0001-8869-768X
Lionel Brétillon
- Fonction : Auteur
- PersonId : 735917
- IdHAL : lionel-bretillon
- ORCID : 0000-0002-6957-100X
- IdRef : 149670303
Niyazi Acar
- Fonction : Auteur
- PersonId : 1136622
- IdHAL : niyazi-acar
- ORCID : 0000-0002-3401-8079
- IdRef : 070519188
Corinne Joffre
- Fonction : Auteur
- PersonId : 747399
- IdHAL : corinne-joffre
- ORCID : 0000-0001-8327-3554
- IdRef : 12845606X
Guillaume Ferreira
- Fonction : Auteur
- PersonId : 804521
- IdHAL : guillaume-ferreira
- ORCID : 0000-0001-5984-8143
- IdRef : 136818978
Raluca Uricaru
- Fonction : Auteur
- PersonId : 1202
- IdHAL : ruricaru
- ORCID : 0000-0002-5730-6428
- IdRef : 151193681
Pierre Gressens
- Fonction : Auteur
- PersonId : 757208
- ORCID : 0000-0002-0909-4221
- IdRef : 066987458
Sophie Layé
- Fonction : Auteur
- PersonId : 747372
- IdHAL : sophie-laye
- ORCID : 0000-0002-3843-1012
- IdRef : 11366883X
Résumé
Westernization of dietary habits has led to a progressive reduction in dietary intake of n-3 polyunsaturated fatty acids (n-3 PUFAs). Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental disorders, conditions in which myelination processes are abnormal, leading to defects in brain functional connectivity. Only little is known about the role of n-3 PUFAs in oligodendrocyte physiology and white matter development. Here, we show that lifelong n-3 PUFA deficiency disrupts oligodendrocytes maturation and myelination processes during the postnatal period in mice. This has long-term deleterious consequences on white matter organization and hippocampus-prefrontal functional connectivity in adults, associated with cognitive and emotional disorders. Promoting developmental myelination with clemastine, a first-generation histamine antagonist and enhancer of oligodendrocyte precursor cell differentiation, rescues memory deficits in n-3 PUFA deficient animals. Our findings identify a novel mechanism through which n-3 PUFA deficiency alters brain functions by disrupting oligodendrocyte maturation and brain myelination during the neurodevelopmental period.