|Title||N-3 PUFA deficiency disrupts oligodendrocyte maturation and myelin integrity during brain development.|
|Publication Type||Journal Article|
|Year of Publication||2022|
|Auteurs||Leyrolle, Q, Decoeur, F, Dejean, C, Brière, G, Leon, S, Bakoyiannis, I, Baroux, E, Sterley, T-L, Bosch-Bouju, C, Morel, L, Amadieu, C, Lecours, C, St-Pierre, M-K, Bordeleau, M, De Smedt-Peyrusse, V, Séré, A, Schwendimann, L, Grégoire, S, Bretillon, L, Acar, N, Joffre, C, Ferreira, G, Uricaru, R, Thebault, P, Gressens, P, Tremblay, M-È, Layé, S, Nadjar, A|
|Date Published||2022 01|
|Keywords||Animals, Brain, Fatty Acids, Omega-3, Mice, Myelin Sheath, Neurogenesis, Oligodendroglia|
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.