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]

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.

Mots clés: Clemastine; Cognition; Hippocampus; Myelin; N-3 PUFA; Neurodevelopement; Oligodendrocyte; Omega-3; Prefrontal cortex

Domaines: Neurosciences [q-bio.NC]

Quentin Leyrolle, Fanny Decoeur, Cyril Dejean, Marie-Galadriel Briere, Stephane Leon, et al.. N‐3 PUFA deficiency disrupts oligodendrocyte maturation and myelin integrity during brain development. Glia, 2022, 70 (1), pp.50-70. ⟨10.1002/glia.24088⟩. ⟨hal-03347586⟩