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Effects of a polyphenol mix from grape and blueberry, the NeurophenolTM extract, on learning and memory performances in aged mice (Julien BENSALEM)

Director of thesis : Pr.Véronique Pallet

Laboratory of Sophie Layé : NutriNeurO

Team of Véronique Pallet : Nutrition, récepteurs nucléaires et vieillissement cérébral

Jury :

Pr Jean-Louis GUILLOU, Professor, Université de Bordeaux, Président

Pr Jeremy SPENCER, Professor, University of Reading, Rapporteur

Pr Frédéric CALON, Professor, Université de Laval, Québec, Rapporteur

Dr David VAUZOUR, PHD, University of East Anglia, Norwich, Examinateur

Pr Véronique PALLET, Professor, INP, Bordeaux, Directrice de thèse

Dr Pauline LAFENETRE, assistant professor, INP, Bordeaux, Invitée

Mr David GAUDOUT, Directeur recherche et innovation, Activ’Inside, Libourne, Invité

ABSTRACT

It is now well accepted that aging is linked to the onset of cognitive impairments. Among them, age-related memory alterations can be brought in evidence both in humans and animals. Several studies have highlighted the beneficial role of polyphenols on memory functions and particularly on age-related memory decline.

            Thus, the Neurophenols project aims at developing nutritional assets rich in polyphenols from grape and blueberry, and to objectify their beneficial role on the age-related cognitive decline in humans and pets.

            The aim of this thesis was to highlight beneficial effects of a polyphenol mix from grape and blueberry, the Neurophenol^TM extract, on learning and memory performances in aged mice and to better understand the neurobiological mechanisms underlying these performances. More specifically, we have focused on the hippocampus, a key brain structure involved in learning and memory processes that is particularly altered during aging. This preclinical work will subsequently objectify the results in humans.

            Our main results show that hippocampal-dependent learning and memory alterations during aging are recovered by a polyphenol supplementation. We also show that these age-related memory deficits are linked to a decrease of gene expression of proteins involved in signaling pathways underlying memory processes and to a decrease of hippocampal neurogenesis. The polyphenol supplementation can restore the expression level of some genes and up-regulate neurotrophin expression in the hippocampus. Moreover, this supplementation has a beneficial impact on hippocampal neurogenesis in aged mice. Finally, we show that a Neurophenol^TM supplementation can reduce mortality in aged mice.

            These results demonstrate the efficiency of the mix Neurophenol^TM on the maintenance of memory performances in mice during aging, through their action on synaptic plasticity and neurogenesis.

            These promising results in aged mice provide positive arguments on the benefits of polyphenols on memory during aging. Thus, it was also developed a clinical study aiming at supplementing elderly subjects with the Neurophenol^TM extract in order to evaluate their memory performances.

Key words: Polyphenols, Grape, Blueberry, Neurophenol^TM, Aging, Learning, Memory, Hippocampus, Synaptic plasticity, Neurogenesis, Lifespan, Mice, Human, Clinical study