Fanny Decoeur PhD

Abstract

Perinatal dietary intakes of n-3 and n-6 polyunsaturated fatty acids (n-3 and n-6 PUFAs), commonly known as omega-3 and omega-6, are essential for brain development. These fatty acids cannot be synthesized by our body and must therefore be provided by the diet in a ratio of one n-3 PUFA for four n-6 PUFAs. In Western countries, the continuous decrease in n-3 PUFA intake for decades is significantly correlated with the increasing incidence of neurodevelopmental diseases, pathologies in which myelination processes are strongly affected. However, at the beginning of my thesis work, very little data was available on the role of PUFAs in the regulation of oligodendrocyte and myelin function.

The main objective of my thesis was to study the potential link between n-3 PUFA deficiency and alterations in the myelination process and the mechanisms involved, with a particular emphasis on microglia/myelin interactions.

Our work shows that perinatal n-3 PUFA deficiency leads to 1) an alteration of white matter associated microglia and oligodendrocyte maturation during brain development; 2) impaired oligodendrocyte functions and microglia/myelin interactions; 3) deficits in the myelination process, associated with thinning of the myelin sheath and ultrastructure alterations; 4) deficits in learning, sociability, and anxious behaviors. Moreover, promoting myelination with pharmacological agents rescued memory deficits in n-3 PUFA deficient mice.

Overall, the present work has clarified some of the mechanisms by which n-3 PUFA deficiency affects the developing brain by highlighting its detrimental effect on microglia and oligodendrocyte and their function especially postnatal myelination. These results are associated with behavioral abnormalities, similar to those observed in models of neurodevelopmental disorders.

Keywords: PUFA, NEURODEVELOPMENT, OLIGODENDROCYTE, MYELIN, MICROGLIA.

Jury

Mme DARNAUDERY Muriel, Professeure, Université de Bordeaux, Présidente

Mme ZUJOVIC Violetta, CR1, INSERM, Rapportrice

M. CALON Frédéric, Professeur titulaire, Université Laval, Rapporteur 

M. PASCUAL Olivier, CRCN, INSERM, Examinateur

Mme NADJAR Agnès, Professeure, Université Bordeaux, Directrice de thèse 

Mme TREMBLAY Marie-Ève, Professeure agrégée, Victoria University, Co-directrice de thèse