CF202543556
ROLE OF POLYUNSATURATED FATTY ACIDS ON MICROGLIA METABOLIC MATURATION DURING NEURODEVELOPMENT.
D-4
Doctorate Full Doctorate
Nouvelle-Aquitaine
Disciplines
Laboratory
UMR 1286 Nutrition et Neurobiologie Intégrée
Host institution
Université de Bordeaux
Doctoral school
Health and life sciences - ED 154

Description

The postnatal developmental period is critical for the optimal maturation of the mammalian brain, involving programmed apoptosis mechanisms to eliminate excess cells and sculpt neuronal networks. Understanding the cellular mechanisms underlying brain maturation could help preventing neurodevelopmental disruptions. Microglia, innate immune cells within the brain, play a key role in shaping neuronal networks via direct phagocytic contact. Microglia also communicate with cerebral cells via extracellular vesicles, containing essential molecular information (protein, lipids, etc). Long chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic acid (AA, n-6) and docosahexaenoic acid (DHA, n-3) are essential for membrane structure, cell signaling and communication, accumulating significantly during early postnatal brain development. Reduced intake of n-3 PUFAs may pose a risk for neurodevelopmental disorders impacting microglial function and brain development. This project aims at understanding LC-PUFA-dependent mechanisms regulating human microglia lipid maturation and their functions during postnatal brain development.

Skills required

Basics in cell biology, neurosciences and/or nutrition and/or neuroimmunology; no apprehension to work with alive animals

Bibliography

1) Madore C, Leyrolle Q, Morel L, Rossitto M, Greenhalgh AD, Delpech JC, Martinat M, Bosch-Bouju C, Bourel J, Rani B, Lacabanne C,Thomazeau A, Hopperton KE, Beccari S, Sere A, Aubert A, De Smedt-Peyrusse V, Lecours C, Bisht K, Fourgeaud L, Gregoire S,Bretillon L, Acar N, Grant NJ, Badaut J, Gressens P, Sierra A, Butovsky O, Tremblay ME, Bazinet RP, Joffre C, Nadjar A, Layé S.Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain. Nat Commun. 2020 Nov30;11(1):6133. doi: 10.1038/s41467-020-19861-z. PMID: 33257673; PMCID: PMC7704669.
2) APOE4 impairs the microglial response in Alzheimer's disease by inducing TGFβ-mediated checkpoints.
Yin Z, Rosenzweig N, Kleemann KL, Zhang X, Brandão W, Margeta MA, Schroeder C, Sivanathan KN, Silveira S, Gauthier C, Mallah D, Pitts KM, Durao A, Herron S, Shorey H, Cheng Y, Barry JL, Krishnan RK, Wakelin S, Rhee J, Yung A, Aronchik M, Wang C, Jain N, Bao X, Gerrits E, Brouwer N, Deik A, Tenen DG, Ikezu T, Santander NG, McKinsey GL, Baufeld C, Sheppard D, Krasemann S, Nowarski R, Eggen BJL, Clish C, Tanzi RE, Madore C, Arnold TD, Holtzman DM, Butovsky O. Nat Immunol. 2023 Nov;24(11):1839-1853. doi:
10.1038/s41590-023-01627-6. Epub 2023 Sep 25. PMID: 37749326
3) Ikezu S, Yeh H, Delpech JC, Woodbury ME, Van Enoo AA, Ruan Z, Sivakumaran S, You Y, Holland C, Guillamon-Vivancos T, YoshiiKitahara A, Botros MB, Madore C, Chao PH, Desani A, Manimaran S, Kalavai SV, Johnson WE, Butovsky O, Medalla M, Luebke JI,Ikezu T. Inhibition of colony stimulating factor 1 receptor corrects maternal inflammation-induced microglial and synaptic dysfunction andbehavioral abnormalities. Mol Psychiatry. 2021 Jun;26(6):1808-1831. doi: 10.1038/s41380-020-0671-2. Epub 2020 Feb 18. PMID:32071385; PMCID: PMC7431382.
4) Madore C, Yin Z, Leibowitz J, Butovsky O. Microglia, Lifestyle Stress, and Neurodegeneration. Immunity. 2020 Feb 18;52(2):222- 240.doi: 10.1016/j.immuni.2019.12.003. Epub 2020 Jan 7. PMID: 31924476;
5) Sex-specific microglia state in the Neuroligin-4 knock-out mouse model of autism spectrum disorder.
Guneykaya D, Ugursu B, Logiacco F, Popp O, Feiks MA, Meyer N, Wendt S, Semtner M, Cherif F, Gauthier C, Madore C, Yin Z, Çınar Ö, Arslan T, Gerevich Z, Mertins P, Butovsky O, Kettenmann H, Wolf SA. Brain Behav Immun. 2023 Jul;111:61-75. doi: 10.1016/j.bbi.2023.03.023. Epub 2023 Mar 29. PMID: 37001827

Keywords

Neurodevelopment, Microglia, Lipid metabolism, fatty acids, human cerebral organoids, extracellular vesicles

Funded offer

Funding type
ANR

Dates

Application deadline 17/05/25

Duration36 months

Start date01/10/25

Creation date18/04/25

Languages

Level of french requiredNone

Level of English requiredNone

Miscellaneous

Annual tuition fee400 € / year

Contacts

You must connect to be able to display the contacts.

click here to connect or register (it's free!)