Leader: Sophie Layé, DR1 INRAE sophie.laye@inrae.fr

Deputy leader: Xavier Fioramonti, CR INRAE xavier.fioramonti@inrae.fr

Team presentation

The general objective of the NutriMind team is to understand how food-derived molecules including nutrients, micronutrients, odorant molecules and bioactive metabolites from the gut microbiota influence neuroimmune interactions and neuronal networks and affect cognitive, emotional and feeding behaviors. To understand the basics of brain nutrient-sensing, we apply translational and integrative approaches ranging from in vitro human and murine iPSC-derived neurons and microglia, ex/in vivo behavioral, electrophysiological, imaging, cellular and molecular approaches using nutritional and transgenic mice models, to human clinic by the collection of dietary supplemented human cohorts including molecular, cellular and cognitive evaluations. These knowledge aim at developing nutrient-based nutritional strategies to prevent and/or delay cognitive dysfunctions in a strategy of personalized nutrition. Our main objectives are to:

1)     Elucidate molecular and cellular mechanisms underlying the behavioral effect of polyunsaturated fatty acids (PUFAs) and their metabolites (oxylipins, ethanolamides), vitamin A, polyphenols, fructose, odorant food-related molecules, microbiota-derived metabolites and complex food molecules 

2)     Depict the neurobiological mechanisms of altered feeding behaviors in the context of unbalanced nutrition

3)     Depict neuroimmune interactions, microglia profile and activity in the developing and aging brain in controlled nutritional conditions

4)     Define neuroprotective mechanisms of food-derived molecules on aging-associated cognitive decline in preclinical models

5)     Define food-derived molecules-based strategies to prevent/delay aging-associated cognitive decline and neurodevelopmental disorders in humans

The discovery of the mechanisms underlying the detrimental or protective effect of nutrition on brain development and aging will allow : to identify new biomarkers for stratification of subjects at risk of neurodevelopmental disorders or cognitive decline; to define novel protective and therapeutic strategies including nutritional and nutrient specific interventions for personalized nutrition; to generate unbiased data for dietary recommendation for the promotion of an healthy brain development and aging; to understand how nutrients/odorant molecules contribute to the regulation of the neurobiology of food intake.

Research axis

Main: 8 Nutrition and Mental Health

Secondary: 1 (Cell biology and development of CNS and synapse cells), 5 (Brain, cognition and behaviour), 6 (Psychiatric pathologies), 7 (Neurodegenerative pathologies), 9 (Neurotechnologies)

Researchers

Jean-Christophe Delpech, CRCN INRAE

David Jarriault, CRCN INRAE

Corinne Joffre, CRHC INRAE

Charlotte Madore-Delpech, CRCN INRAE

Véronique Pallet (Professeur Bordeaux INP)

Anabelle Redonnet (Maître de conférences Université de Bordeaux)

Technicians - Engineers

 Agnès Aubert, TR INRAE

Milan Boulaire, CDD AI Bordeaux INP

Moïra Rossita, CDD IR INRAE

Alexandra Sere, AT Université de Bordeaux

Marjorie Varih, CDD AI INRAE

Postdoctoral fellows

Liam Barry-Carroll

Mathilde Chataigner

Aurélie Ginisty

Quentin Leyrolle

Camille Mougin

PhD Students

Adeline Coursan

Flore Marchaland

Ivan Marniquet

Marie Martin 

Maud Martinat

Publications

1. Madore C., Leyrolle Q., Morel L., Rossitto M., Greenhalgh A.D., Delpech J.C., Martinat M., Bosch-Bouju C., Bourel J., Rani B., Lacabanne C., Thomazeau A., Hopperton K.E., Beccari S., Sere A., Aubert A., De Smedt-Peyrusse V., Lecours C., Bisht K., Fourgeaud L., Gregoire S., Bretillon L., Grant N. J., Badaut J., Gressens P., Sierra A., Butovsky O., Tremblay M.E., Bazinet R.P., Joffre C., Nadjar A. and Layé S. Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the developing brain, Nature Comm, 2020, 11(1):6133.
2. Bazinet R and Layé S., Polyunsaturated fatty acids and their metabolites in brain function and disease, Nature Reviews Neuroscience, 2014, 15(12):771-85
3. Lafourcade M, Larrieu, T., Mato S, Duffaud A, Sepers M, Matias I, De Smedt V, Labrousse V, Bretillon L, Matute C, Rodr√≠guez-Puertas R, Layé S # and Manzoni O# (#, equal contribution), Nutritional Omega-3 deficiency abolishes endocannabinoid mediated neuronal functions, Nature Neuroscience, 2011, 14(3):345-50. 
4. Fulton S, Décarie-Spain L, Fioramonti X, Guiard B, Nakajima S. The menace of obesity to depression and anxiety prevalence. Trends Endocrinol Metab., 2022, 33(1):18-35.
5. Bouyakdan K, Martin H, Liénard F, Budry L, Taib B, Rodaros D, Chrétien C, Biron É, Husson Z, Cota D, Pénicaud L, Fulton S, Fioramonti X, Alquier T. The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system. J Clin Invest., 2019, 129(6):2417-2430.
6. Chataigner M, Mortessagne P, Lucas C, Pallet V, Layé S, Mehaignerie A, Bouvret E, Dinel AL, Joffre C, Dietary fish hydrolysate supplementation containing n-3 LC-PUFAs and peptides prevents short-term memory and stress response deficits in aged mice. Brain Behav Immun, 2021, 91:716-730.
7. Chataigner M, Martin M, Lucas C, Pallet V, Layé S, Mehaignerie A, Bouvret E, Dinel AL, Joffre C, ,Fish Hydrolysate Supplementation Containing n-3 Long Chain Polyunsaturated Fatty Acids and Peptides Prevents LPS-Induced Neuroinflammation. Nutrients, 2021, 13(3):824.
8. Joffre C., Dinel A.L., Chataigner M., Pallet V., Layé S., N-3 polyunsaturated fatty acids and their derivates reduce neuroinflammation during aging. Nutrients, 2020, 12:647.
9. Merle, L., Person, O., Bonnet, P., Grégoire, S., Soubeyre, V., Grosmaitre, X., & Jarriault, D., Maternal high fat high sugar diet disrupts olfactory behavior but not mucosa sensitivity in the offspring. Psychoneuroendocrinology, 2019, 104, 249-258.
10. Ikezu S., Yeh H., Delpech J.C., Woodbury E.M., Van Enoo A.A., Ruan Z., Sivakumaran S., You Y.,Holland C., Guillamon-Vivancos T., Yoshii-Kitahara A., Botros B.M., Madore C., Chao P-h., Desani A., Manimaran S., Kalavai SV, Johnson E.W., Butovsky O., Medalla L., Luebke I.J., Ikezu T. (2021), Inhibition of colony stimulating factor 1 receptor corrects maternal inflammation-induced microglial and synaptic dysfunction and behavioral abnormalities, Mol. Psychiatry, 2021 26:1808.doi: 10.1038/s41380-020-0671-2 
11. Delpech JC, Herron S, Botros MB, Ikezu T. Neuroimmune Crosstalk through Extracellular Vesicles in Health and Disease. Trends Neurosci. 2019 42(5):361-372. 
12. Delpech JC, Pathak D, Varghese M, Kalavai SV, Hays EC, Hof PR, Johnson WE, Ikezu S, Medalla M, Luebke JI, Ikezu T. Wolframin-1-expressing neurons in the entorhinal cortex propagate tau to CA1 neurons and impair hippocampal memory in mice. Sci Transl Med. 2021 15;13(611):eabe8455.