N‐3 PUFA deficiency disrupts oligodendrocyte maturation and myelin integrity during brain development

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Leyrolle, Quentin | Decoeur, Fanny | Dejean, Cyril | Briere, Marie-Galadriel | Leon, Stephane | Bakogiannis, Ioannis | Baroux, Emilie | Sterley, Tony‐lee | Bosch-Bouju, Clémentine | Morel, Lydie | Amadieu, Camille | Lecours, Cynthia | St‐pierre, Marie‐kim | Bordeleau, Maude | de Smedt-Peyrusse, Veronique | Sere, Alexandra | Schwendimann, Leslie | Grégoire, Stéphane | Brétillon, Lionel | Acar, Niyazi | Joffre, Corinne | Ferreira, Guillaume | Uricaru, Raluca | Thebault, Patricia | Gressens, Pierre | Tremblay, Marie‐eve | Layé, Sophie | Nadjar, Agnes

Edité par CCSD ; Wiley -

International audience. 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.

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