ED Sciences de la Vie et de la Santé
Mechanistic role of polyunsaturated fatty acids in brain development and cognitive trajectory
by Flore MARCHALAND (Nutrition et Neurobiologie Intégrée)
The defense will take place at 14h00 - Amphitéâtre du BBS Bâtiment Bordeaux Biologie Santé (BBS) 2 rue Docteur Hoffmann Martinot 33000 Bordeaux
in front of the jury composed of
- Sophie LAYE - Directrice de recherche - Laboratoire de Nutrition et de Neurobiologie Intégrée (NutriNeuro), INRAE UMR 1286, Université de Bordeaux - Directeur de these
- Pascale CHAVIS - Directrice de recherche - Institut de Neurobiologie de la Méditerranée (INMED), INSERM UMR 1249, Université Aix-Marseille - Rapporteur
- Pierre GRESSENS - Professeur - Neurodiderot, INSERM UMR 1141, Université Paris Diderot - Rapporteur
- Emilie PACARY - Chargée de recherche - Neurocentre Magendie, INSERM UMR 1215, Université de Bordeaux - Examinateur
- Daniela COTA - Directrice de recherche - Neurocentre Magendie, INSERM UMR 1215, Université de Bordeaux - Examinateur
- Christoph RUMMEL - Professeur - Institut de physiologie et biochimie vétérinaires, Université Justus Liebig de Giessen - Examinateur
N-3 and n-6 polyunsaturated fatty acids (PUFA) are essential for mammals, as they cannot be synthesized de novo and must therefore be provided by the diet. Once consumed, PUFA are incorporated into cellular membranes, where they play a major structural role. Among PUFA, docosahexaenoic acid (DHA, n-3) and arachidonic acid (ARA, n-6) are long-chain PUFA (LC-PUFA) that are particularly enriched in the brain. They are respectively derived from the metabolism of α-linolenic acid (ALA, n-3) and linoleic acid (LA, n-6), their precursors found in plant-derived foods. LC-PUFA can also be directly supplied by animal-derived foods, primarily marine sources for n-3 and terrestrial sources for n-6. LC-PUFA accumulate in the brain during the perinatal period during which they are transferred from the mother to the infant first via the placenta and subsequently through breast milk. Thus, the supply of LC-PUFA to the infant largely depends on maternal dietary PUFA intake. However, since the late 20th century, changes in dietary habits have led to an increase in n-6 PUFA consumption alongside a decrease in n-3 PUFA intake. Epidemiological and clinical studies have highlighted an inverse correlation between maternal n-3 PUFA dietary intake and children's cognitive performance. Furthermore, experimental studies in rodents have shown that perinatal n-3 PUFA deficiency impairs cognitive functions as well as neuronal morphology and function in male offspring. However, the underlying mechanisms and potential sex-specific differences remain poorly understood. In this context, the primary objective of my PhD research was to investigate the cellular and molecular mechanisms underlying the behavioral and neurobiological effects induced by perinatal n-3 PUFA deficiency in both male and female offspring. Additionally, I examined whether maintaining n-3 PUFA, through an innovative genetic approach, could prevent these alterations. The results obtained indicate that perinatal n-3 PUFA deficiency affects, in some cases in a sex-dependent manner, 1) brain profiles of PUFA and their oxygenated derivatives (oxylipins) ; 2) the trajectory of physical and motor development ; 3) spatial memory ; and 4) long-term synaptic plasticity in the hippocampus. Genetic maintenance of PUFA in offspring exposed to this perinatal n-3 PUFA deficiency enables 1) the prevention of impairments in spatial memory and long-term synaptic plasticity in the hippocampus ; 2) an increase in mature synapse density, particularly glutamatergic synapses, within the hippocampus ; 3) the promotion of a transcriptional signature associated with synapse and neuronal network maturation ; and 4) the generation of a unique brain oxylipin profile differing by sex. In contrast, genetic modulation of PUFA synthesis specifically in CaMKII neurons, which are predominantly glutamatergic, is not sufficient to prevent alterations in the PUFA profile of hippocampal synaptosomes or to rescue memory deficits induced by perinatal n-3 PUFA deficiency. Finally, this work also shows that perinatal n-3 PUFA deficiency alters the transcriptomic signature of hippocampal microglia only from three weeks after birth, with no significant effects observed earlier in development, in a sex-dependent manner. Overall, my PhD work has shed light on the mechanisms by which perinatal n-3 PUFA deficiency impairs brain development and cognition, disrupting synaptic and neuronal network maturation in the hippocampus at both the cellular and molecular levels.
ED Sociétés, Politique, Santé Publique
From building proximity to collective activity: the work of managers in light of their interactions. Contributions of a research-intervention in ergonomics within a logistics center.
by Claire VIOLLEAU (Laboratoire de l'Intégration du Matériau au Système)
The defense will take place at 14h00 - Amphi Jean Paul Dom - A0.85 IMS - Bâtiment A31 - 351 cours de la Libération - 33405 Talence Cedex
in front of the jury composed of
- Johann PETIT - MCF - HDR - Université de Bordeaux - Directeur de these
- Sandrine CAROLY - Professeur - Université Grenoble Alpes - Rapporteur
- Flore BARCELLINI - Professeur - CNAM Paris - Rapporteur
- Pascal UGHETTO - Professeur - LATTS, université Gustave-Eiffel - Examinateur
- Mathieu DETCHESSAHAR - Professeur - IAE de l'Université de Nantes - Examinateur
Managers are regarded as major players in organizations, both from a performance and health perspective, as they implement regulations to manage inevitable variability. The aim of this research-intervention is to study the managers' work on regulations by analyzing their activity through the prism of their interactions. It involves some twenty managers on four hierarchical levels in a logistics warehouse of a multinational retailer. We begin by describing the way in which managers construct and develop their proximity to the real work of the teams they supervise, by focusing on their interactions with their subordinates, whether direct or mediated. We then extend the study of these interactions to all stakeholders, and we analyze the various forms of collective activity managers develop to respond to the preoccupations caused by their activity. By showcasing the conditions, the effects and the interdependencies of their activity, our results contribute to a better understanding of their work, and shed light on the chains of regulation between hierarchical levels. Finally, as managers are usually more studied for the effects they have on the health of others than for themselves, these results open up new perspectives on how to encourage and support the development of their activity.