Venue: Centre Broca
Defense in french
Marie Martin
NutriNeuro
Thesis supervisor: Corinne Joffre
Title
Effect of a plant extracts and omega-3 combination on biological processes involved in age-related cognive decline
Abstract
Population’s aging represents one of the world’s greatest economic, societal and public health challenges. By 2050, more than a billion people worldwide will be aged 60 or over, making it all the more important to age well. In this context, age-related cognitive decline, characteristic of aging, is a critical factor to be considered in order to improve the quality of life of the elderly and prevent loss of autonomy. One promising approach is to propose nutritional strategies. Among existing bioactive nutrients, polyphenols from berries (grapes, blueberries), saffron compounds and n-3 polyunsaturated fatty acids (n-3 PUFAs) from fish are recognized for their beneficial properties on memory functions. The aim of this thesis was to evaluate the efficacy of a combination of these nutrients in preventing age-related cognitive decline, and to understand the neurobiological mechanisms involved. We targeted the hippocampus, a key brain structure involved in memory processes and particularly impaired during aging. Our main results showed that a combination of berry polyphenols, saffron compounds and n-3 PUFA extracts in aged mice effectively prevented both short- and long-term memory impairment. These results were associated with improved neuronal plasticity and neurogenesis, including an increase in DCX, a marker of immature neurons, and up-regulation of signalling pathways involved in synaptic development and function. These beneficial effects can be explained by the modulation of several key biological processes. Indeed, the nutrient combination showed a powerful anti-inflammatory effect by regulating inflammatory lipid mediators, notably pro-resolving oxylipins (18-HEPE, 17-HDHA, 14-HDHA) in adult mice during of acute inflammation, and by inhibiting inflammation-related signaling pathways in aged mice during of chronic inflammation. In addition, it limited oxidation by increasing the expression of antioxidant enzymes such as catalase, superoxide dismutase and glutathione peroxidase in adult mice in response to acute inflammation or treatment inducing accelerated aging, and by inhibiting oxidative stress-related signalling pathways in aged mice. We also demonstrated that the gut microbiota may play an important role in these effects via the gut-brain axis. In particular, we have demonstrated an increase in bacteria favorable to cognitive health, and a decrease in those associated with inflammation and memory impairment. Finally, this work has enabled us to identify a pool of genes whose expression was increased during aging in the hippocampus and was negatively correlated with cognitive performance. These genes could serve as biomarkers of cognitive decline. Interestingly, their expression was diminished by the combination of nutrients. Thus, our study demonstrates that the combination of berry polyphenols, bioactive saffron compounds and fish n-3 PUFAs prevents memory impairment by acting on various major neurobiological processes of aging. This multi-targeted nutritional approach has great potential for preventing age-related cognitive decline and promoting healthy aging. These results pave the way for new nutrition-based preventive strategies to combat the effects of cerebral aging.
Keywords: aging, nutrition, polyphenols, saffron, n-3 PUFA, memory.
Publications
Martin M, Boulaire M, Lucas C, Peltier A, Pourtau L, Gaudout D, Layé S, Pallet V, Joffre C, Dinel AL.
Plant Extracts and ω-3 Improve Short-Term Memory and Modulate the Microbiota-Gut-Brain Axis in D-galactose Model Mice.
J Nutr. 2024 Sep 25:S0022-3166(24)01032-0.
doi: 10.1016/j.tjnut.2024.09.015.
Epub ahead of print. PMID: 39332773.
Martin M, Debenay E, Bardinet J, Peltier A, Pourtau L, Gaudout D, Layé S, Pallet V, Dinel AL, Joffre C.
Plant extracts and omega-3 supplementation modulate hippocampal oxylipin profile in response to LPS-induced neuroinflammation.
Inflamm Res. 2024 Sep 28.
doi: 10.1007/s00011-024-01947-9.
Epub ahead of print. PMID: 39340661.
Jury
Mme Corinne JOFFRE, Directrice de recherche, UMR Nutrineuro, INRAE, Bordeaux Directrice de thèse
Mme Aurélie DE RUS JACQUET, Professeure adjointe, Université Laval, Québec, CANADA Rapportrice
M. Niyazi ACAR, Directeur de recherche, UMR CGSA, INRAE, Dijon Rapporteur
Mme Virginie AIRES, Maîtresse de conférences, Université de Bourgogne, Dijon Examinatrice
M. Frédéric CALON, Professeur, Université Laval, Québec, CANADA Examinateur
Mme Agnès NADJAR, Professeure, Université de Bordeaux, Bordeaux Examinatrice
Membres invités
Dr. Line POURTAU, Responsable Recherche & Développement, Activ’Inside, Bordeaux Invitée
Dr. Anne-Laure DINEL, Docteur, ADERA, Bordeaux Invitée