Venue: to be confirmed
Defense in french
Thesis supervisor: Sophie Layé (NutriNeuro)
Title
Oméga 3 et troubles de l’humeur : mécanismes d’action neuroprotecteurs (Omega 3 and mood disorders, study of neuroprotective actions mechanisms)
Résumé
The brain is rich in polyunsaturated fatty acids (PUFA) whose long chains, such as docosahexaenoic acid (DHA) and ecosapentaenoic acid (EPA) from omega 3 (n–3), accumulate during development. Their precursors are not synthesized de novo by mammals and must be provided by food. However, it has been shown that an unbalanced and deficient maternal dietary intake of n–3 PUFAs induces cognitive
and electrophysiological alterations in infants and in mouse models of nutritional deficiency.
We are interested in the impact of a nutritional intervention during development and how a diet unbalanced in n–3 PUFA alters neural networks and cognition, by studying the molecular mechanisms and taking into account the gender. To this end, different models are used: 1) mice are deficient in PUFAs during development and then exposed to a diet rich in n–3 PUFAs at weaning; 2) to develop a local deficiency model by viral injection blocking the expression of the elongase ELOVL2 (involved in the synthesis of long–chain PUFAs) in astrocytes to assess the impact on the properties of the surrounding neurons.
Our results suggest that a change in nutritional status from deficiency to a diet rich in n–3 PUFA at weaning restores 1) long–term synaptic plasticity in the hippocampus in males and females, 2) cognition as well as fatty acid levels in the brain but in a differential manner between the two sexes. In the second part of the results, a local variation of PUFA synthesis in the astrocyte modifies the excitability of neurons without modifying the levels of fatty acids in the brain structure while modifying some criteria of emotional behavior.
Key words: PUFA, developpment, cognition, neuroprotection
Jury
Pr Mélanie Plourde, Professeure, Université de Sherbrooke, Québec, Canada, Rapportrice
Dr Pascale Chavis, Directrice de Recherche, Inmed, Marseille, France, Rapportice
Dr Niyazi Acar, Directeur de Recherche, INRAE, Dijon, France, Examinateur
Pr Frédéric Calon, Professeur, Université de Laval, Canada, Président, Examinateur
Pr Richard Bazinet, Professeur Associé, Université de Toronto, Canada, Co-directeur
Dr Sophie Layé, Directrice de Recherche, INRAE, Bordeaux, France, Directrice