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The influence of hormonal signals on brain development, neurodegenerative diseases and cognitive impairment.

from basic science:
  • Endocrinology
  • Neurobiology
to the translational research:
  • Neurodegenerative diseases
  • Aging-related diseases
  • Cognitive impairme
Franck Oury
Integrative Neurobiology

Scientific background: I am graduated in neurobiology (2007) from Louis Pasteur University-Strasbourg (France), where I studied neuro-developmental biology in the laboratory of Filippo Rijli at Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC). My doctoral work demonstrated the crucial role of the homeobox transcription factors for the establishment of the sensory neuronal connectivity. I then moved to Columbia University – Medical Center, New York, USA, in the laboratory of Gerard Karsenty, where I gained expertise in neuro- and integrative-physiology, identifying novel endocrine functions of the skeleton in regulating gonadal, pancreatic and brain functions. In 2014, I decided to join the Institut Necker Enfants-Malades (INEM) in Paris to start my own group. I obtained a permanent INSERM position as CR1 in 2014 and as DR2 in 2019. My work is currently supported by the ATIP-Avenir, HFSP, FRM, ANR, INERM transfer, Allianz, Emergence de la ville de Paris, European foundation of diabetes, AGEMED et FSER program.

His team is currently using an interdisciplinary approach (neurobiology, cell biology, endocrinology and integrative physiology) to study to understand how brain functions are modulated by hormonal factors. Dr. Oury's laboratory recently contribute to the demonstration that the systemic factors are essential for the maintenance of the neuronal homeostasis, the brain plasticity and cognitive fitness. Among these factors, they identified Osteocalcin (Ocn): a bone derived hormone that plays an important role in regulating hippocampal-dependent memory and brain aging process. The most recent work of the team demonstrates that autophagy is a necessary mechanism to mediate the communication between circulating factors and hippocampal neurons and that pharmacological modulation of neuronal autophagy is able to improve memory deficits observed in aged mice. His laboratory has now a particular interest in developing novel therapeutic strategies to treat age-related cognitive disorders and associated diseases.

FUNDING (Research Grants, Fellowships, Scholarships)

  • Foundation NRJ for neuroscience – (2020-2021) (Coordinator)
  • AgeMED 2.0 – Aging Program INSERM (2020-2024) (Coordinator)
  • European foundation of study of Diabetes (EFSD) award, EU (2020-2021) (Coordinator)
  • Fondation pour la Recherche Médicale (FRM) – – Team labellisation (2019-2022) (Coordinator)
  • ANR « Memorautophagy » Grant (2018-2021) (Coordinator)
  • CoPOC INSERM Transfert (2017-2018) (Coordinator)
  • FSER (2017-2020) (Coordinator)
  • AgeMED – Aging Program INSERM (2016-2021) (Coordinator)
  • Emergence de la ville de Paris (2016) (Coordinator)
  • ATIP-AVENIR Program, INSERM-CNRS (2015) (Coordinator)
  • Human Frontiers Science Program (HFSP), Career Developmental Award (CDA) (2015) (Coordinator)
  • Fondation pour la Recherche Médicale (FRM) - Amorçage Jeunes Equipes (2014) (Coordinator)

AWARDS

  • Foundation Necker Award, France (2020)
  • Foundation NRJ for neuroscience, France (2020)
  • Allianz-ADPS Longevity Research Award, France (2019)
  • ECTS Iain T Boyle award (The European Calcified Tissue Society), Spain (2018)
  • Science and Technology in Society Forum (STS forum) award, Japan (2016)
  • Fondation Schlumberger pour la Recherche et l’Education award (FSER) (2016) (Coordinator)
  • Rupert Timpl Award – International Society for Matrix Biology (2014)
  • Blavatnik Award – The New York Academy of Sciences-Best young investigator East Coast (USA) (2011)
  • ASBMR – Young investigator Award (USA) (2010)
  • Foundation Philippe (France-USA) (2007)
  • Foundation Bettencourt-Schueller, Young Investigator Award (2007)

Focus

The main focus of my laboratory is to investigate the roles played by hormonal factors on the regulation of brain cognitive functions in normal, pathological and aging conditions.

Introduction

Hormones are essential factors ensuring proper regulation of our physiological functions by mediating dialogue between organs. Their broad spectrum of actions is not limited to the peripheral organs. Some hormonal factors, such as leptin, insulin, thyroid hormones, steroid hormones reach the central nervous system (CNS) where they modulate the central regulation of whole-body metabolism.

Recently, it has been shown that they can also influence more intrinsic functions of the CNS, such as brain development, adult neurogenesis and cognitive functions. Importantly, increasing evidence suggests that changes in their circulating levels may contribute to age-related cognitive decline, as well as to the development of neurodegenerative diseases. While the functional importance of hormonal factors on brain activities is undeniable, their cellular and molecular mechanisms of action are unclear. Moreover, although the brain expresses receptors for most, if not all, hormonal factors, the role(s) of many hormones in the CNS remain unexplored. Characterizing the influence of hormonal homeostasis during aging may open up new roads for therapeutic intervention to ameliorate age- and disease-related cognitive impairments, and reverse/prevents age-related memory decline.

Research objectives

While it is evident that hormonal factors are essential to mediate communication between our peripheral organs and the central nervous system, we have an imcomplete understanding of the roles played by hormonal factors in controling brain metabolic and cognitive functions (in healthy and aging population).

The overall research goals of my laboratory are:

  1. To determine additional hormonal signaling pathways regulating brain cognitive and metabolic functions
  2. To identify the molecular and cellular mechanisms mediating hormonal regulation of brain functions
  3. To explore the causality between hormonal imbalances and the decline of cognitive functions during aging

We are currently using an interdisciplinary approach that combines mouse genetics, cellular and molecular methodologies, local brain stereotactic injections, lentiviral-based gene downregulation, primary neuronal cells-based assays, and behavioral/metabolic analyses, to answer these questions. For the translational aspects of my projects, we have multiple collaborations with clinicians at Paris Descartes-Sorbone Cité campus.

Main publications

  1. Glatigny M, Moriceau S, Rivagorda M, Ramos-Brossier M, Nascimbeni AC, Lante F, Boudarene N, Friedman AK, Kuperwasser N, Friedlander G, Buisson A, Morel E, Codogno P, and Oury F*.
    Autophagy is required for memory formation and reverses age-related memory declines.
    Current Biology. 2019. 29(10):1-14. IF: 11,25. (>40 citations) - (2 highlights in Faculty 1000)
  2. Khrimian L, Obri A, Ramos-Brossier M, Rousseaud A, Moriceau S, Mera P, Kosmidis S, Karnavas T, Gao XB, Oury F*, Kandel E, and Karsenty G*.
    Gpr158 mediates osteocalcin’s regulation of cognition.
    J Exp Med. 2017. 214(10):2859-73. IF: 12,79. (>100 citations)
  3. Ferron M, Lacombe J, Germain A, Oury F, Karsenty G.
    GGCX and VKORC1 inhibit osteocalcin endocrine functions.
    J Cell Biol. 2015; 208(6):761-76. IF: 11,78. (>90 citations)
  4. Oury F, Khrimian L, Gardin A, Chamouni A, Goeden N, Huang Y, Lee H, Srinivas P, Gao XB, Suyama S, Mann JJ, Horvath T, Bonnin A, Karsenty G.
    Maternal and offspring pools of osteocalcin influence brain development and functions.
    Cell. 2013.155(1):228-41. IF: 30.987. (>250 citations) - (2 highlights in Faculty 1000)
  5. Oury F, Ferron M, Xu L, Confavreux C, Srinivas P, Lacombe J, Wang H, Chamouni A, Lugani F, Lejeune H, Kumar TR, Plotton I, Karsenty G.
    Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis.
    J Clin Invest. 2013.123(6):2421-33. IF: 13,25. (>190 citations)
  6. Oury F, Sumara G, Sumara O, Ferron M, Chang H, Smith C.E, Hermo l, Suarez S, Roth B.L, Ducy P, Karsenty G.
    Endocrine regulation of male fertility by skeleton.
    Cell. 2011. 144(5):796-809. IF: 30.987. (>500 citations) - (8 highlights in Faculty 1000)
  7. Yadav VK*, Oury F *, Tanaka K, Thomas T, Wang Y, Cremers S, Schutz G, Hen R, Krust A, Chambon P, Karsenty G.
    Leptin-dependent serotonin control of appetite: temporal specificity, transcriptional mediation and therapeutic implications.
    J Exp Med. 2011. 208(1):41-52. IF: 10,79. (>100 citations)
  8. Oury F, Yadav VK, Wang Y, Guo E, Schutz G, Means A. Karsenty G.
    CREB mediates the brain-derived serotonin regulation of bone mass accrual.
    Genes and Dev. 2010. 11(3):231-238. IF: 9,41. (>100 citations)
  9. Oury F, Yadav VK, Suda N, Liu ZW, Gao XB, Confavreux C, Klemenhagen KC, Tanaka KF, Gingrich JA, Guo WE, Tecott LH, Mann JJ, Hen R, Horvath TL and Karsenty G.
    A Serotonin-Dependent Mechanism Explains the Leptin Regulation of Bone Mass, Appetite, and Energy Expenditure.
    Cell. 2009. 138, Issue 5, 976-989. IF: 30.987. (>650 citations) - (4 highlights in Faculty 1000)
  10. Oury F, Murakami Y, Renaud JS, Pasqualetti M, Charnay P, Ren SY, and Rijli FM.
    Hoxa2- and Rhombomere-Dependent Development of the Mouse Facial Somatosensory Map.
    Science. 2006. 313(5792):1408-13. IF: 37,20. (>200 citations) - (2 highlights in Faculty 1000)

Five major original publications

  • Siopi E., Galerne M., Rivagorda M., Saha S., Moigneu C., Moriceau S., Bigot M., Oury F., Lledo P-M. (2023). Gut microbiota changes require vagus nerve integrity to promote depressive-like behaviors in mice. Mol Psychiatry. May 2. doi: 10.1038/s41380-023-02071-6. Online ahead of print. 
  • Cornille M., Moriceau S., Khonsari R.H., Heuzé Y., Loisay L., Boitez V., Morice A., Arnaud E., Collet C., Bensidhoum M., Kaci N., Boddaert N., Paternoster G., Rauschendorfer T., Werner S., Mansour S.L., Di Rocco F., Oury F., Legeai-Mallet L. (2022). FGFR3 over-activation in the brain is responsible for memory impairments in Crouzon syndrome mouse model. J Exp Med. Apr 4;219(4):e20201879. doi: 10.1084/jem.20201879.
  • De Risi M., Torromino G., Tufano M., Moriceau S., Pignataro A., Rivagorda M., Carrano N., Middei S., Settembre C., Ammassari-Teule M., Gardoni F., Mele A., Oury F., De Leonibus E. (2020). Mechanisms by which autophagy regulates memory capacity in ageing. Aging Cell. Sep;19(9):e13189. doi: 10.1111/acel.13189.
  • Glatigny M., Moriceau S., Rivagorda M., Ramos-Brossier M., Nascimbeni A.C., Lante F., Shanley M.R., Boudarene N., Rousseaud A., Friedman A.K., Settembre C., Kuperwasser N., Friedlander G., Buisson A., Morel E., Codogno P., Oury F. (2019). Autophagy is required for memory formation and reverses age-related memory declines. Current Biology. Feb 4;29(3):435-448.e8. doi: 10.1016/j.cub.2018.12.021.
  • Khrimian L., Obri A., Ramos-Brossier M., Rousseaud A., Moriceau S., Nicot A-S., Mera P., Kosmidis S., Karnavas T., Saudou F., Gao X-B., Oury F., Kandel E., Karsenty G. (2017). Gpr158 mediates osteocalcin’s regulation of cognition. J Exp Med. Oct 2;214(10):2859-2873. doi: 10.1084/jem.20171320.
  • List of publications

    2020

  • De Risi M, Torromino G, Tufano M, Moriceau S, Pignataro A, Rivagorda M, Carrano N, Middei S, Settembre C, Ammassari-Teule M, Gardoni F, Mele A, Oury F, De Leonibus E.
    Mechanisms by which autophagy regulates memory capacity in ageing.
    Aging Cell. 2020 Jul 30;19(9):e13189. doi: 10.1111/acel.13189
  • Fregeac J£, Moriceau S£, Poli A, Nguyen LS, Oury F* and Colleaux L*.
    Loss of the neurodevelopmental disease-associated gene miR-146a impairs neural progenitor differentiation and causes learning and memory deficits.
    Molecular Autism. 2020. 30(1):22.
  • Joseph A£, Moriceau S£, Sica V, Anagnostopoulos G, Pol J, Martins I, Lafarge A, Maiuri MC, Magnan C, Leboyer M, Bravo-San Pedro JM, Oury F, Kroemer G.
    Metabolic and psychiatric effects of acyl coenzyme A binding protein (ACBP)/diazepam binding inhibitor (DBI)
    Cell Death Dis. 2020 Jul 6;11(7):502. doi: 10.1038/s41419-020-2716-5
  • 2019

  • Glatigny M, Moriceau S, Rivagorda M, Ramos-Brossier M, Nascimbeni AC, Lante F, Shanley MR, Boudarene N, Rousseaud A, Friedman AK, Settembre C, Kuperwasser N, Friedlander G, Buisson A, Morel E, Codogno P, Oury F.
    Autophagy Is Required for Memory Formation and Reverses Age-Related Memory Decline.
    Curr Biol. 2019 Feb 4;29(3):435-448.e8. doi: 10.1016/j.cub.2018.12.021. Epub 2019 Jan 17.
  • Ferron M, Lacombe J, Germain A, Oury F, Karsenty G.
    GGCX and VKORC1 inhibit osteocalcin endocrine functions.
    J Cell Biol. 2019 Jun 3;218(6):2071. doi: 10.1083/jcb.20140911104082019c.
  • Gonçalves TJM, Boutillon F, Lefebvre S, Goffin V, Iwatsubo T, Wakabayashi T, Oury F, Armand AS.
    Collagen XXV promotes myoblast fusion during myogenic differentiation and muscle formation.
    Sci Rep. 2019 Apr 10;9(1):5878. doi: 10.1038/s41598-019-42296-6.
  • Ureña-Torres PA, Vervloet M, Mazzaferro S, Oury F, Brandenburg V, Bover J, Cavalier E, Cohen-Solal M, Covic A, Drüeke TB, Hindié E, Evenepoel P, Frazão J, Goldsmith D, Kazama JJ, Cozzolino M, Massy ZA.
    Novel insights into parathyroid hormone: report of The Parathyroid Day in Chronic Kidney Disease.
    Clin Kidney J. 2018 Jul 20;12(2):269-280. doi: 10.1093/ckj/sfy061. eCollection 2019 Apr.
  • 2018

  • Obri A, Khrimian L, Karsenty G, Oury F.
    Osteocalcin in the brain: from embryonic development to age-related decline in cognition.
    Nat Rev Endocrinol. 2018 Mar;14(3):174-182. doi: 10.1038/nrendo.2017.181. Epub 2018 Jan 29. Review.
  • Oury J, Oury F.
    Osteocalcin, a key molecule for bone endocrine functions
    Med Sci (Paris). 2018 Jan;34(1):54-62. doi: 10.1051/medsci/20183401014. Epub 2018 Jan 31. Review. French.
  • 2017

  • Khrimian L, Obri A, Ramos-Brossier M, Rousseaud A, Moriceau S, Nicot AS, Mera P, Kosmidis S, Karnavas T, Saudou F, Gao XB, Kandel E, Oury F, Karsenty G. Gpr158 mediates osteocalcin's regulation of cognition. J Exp Med. 2017 Oct 2;214(10):2859-2873. doi: 10.1084/jem.20171320. Epub 2017 Aug 29
  • 2016

  • Rousseaud A, Moriceau S, Ramos-Brossier M, Oury F. Bone-brain crosstalk and potential associated diseases. Horm Mol Biol Clin Investig. 2016 Nov 1;28(2):69-83.
  • 2015

  • Chamouni A, Schreiweis C, Oury F. Bone, brain & beyond. Rev Endocr Metab Disord. 2015 Rev Endocr Metab Disord. 2015 Jun;16(2):99-113.
  • Ferron M, Lacombe J, Germain A, Oury F, Karsenty G. GGCX and VKORC1 inhibit osteocalcin endocrine functions. J Cell Biol. 2015 Mar 16; 208(6):761-76.
  • 2014

  • Chamouni A, Oury F. Reciprocal interaction between bone and gonads. Arch Biochem Biophys. 2014 Nov 1;561:147-53.
  • Karsenty G, Oury F. Regulation of male fertility by the bone-derived hormone osteocalcin. Mol Cell Endocrinol. 2014 Jan 25;382(1):521-6.
  • 2013

  • Oury F, Khrimian L, Denny CA, Gardin A, Chamouni A, Goeden N, Huang YY, Lee H, Srinivas P, Gao XB, Suyama S, Langer T, Mann JJ, Horvath TL, Bonnin A, Karsenty G. Maternal and offspring pools of osteocalcin influence brain development and functions. Cell. 2013 Sep 26;155(1):228-41.
  • Oury F, Ferron M, Huizhen W, Confavreux C, Xu L, Lacombe J, Srinivas P, Chamouni A, Lugani F, Lejeune H, Kumar TR, Plotton I, Karsenty G. Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis. J Clin Invest. 2013 Jun;123(6):2421-33. Erratum in: J Clin Invest. 2015 May;125(5):2180.
  • 2012

  • Oury F. A crosstalk between bone and gonads. Ann N Y Acad Sci. 2012 Jul;1260:1-7. doi: 10.1111/j.1749-6632.2011.06360.x. Review.
  • Karsenty G, Oury F. Biology without walls: the novel endocrinology of bone. Annu Rev Physiol. 2012;74:87-105. doi: 10.1146/annurev-physiol-020911-153233. Review.
  • 2011

  • Oury F, Karsenty G. Towards a serotonin-dependent leptin roadmap in the brain. Trends Endocrinol Metab. 2011 Sep;22(9):382-7.
  • Oury F, Sumara G, Sumara O, Ferron M, Chang H, Smith CE, Hermo L, Suarez S, Roth BL, Ducy P, Karsenty G. Endocrine regulation of male fertility by the skeleton. Cell. 2011 Mar 4;144(5):796-809.
  • Yadav VK, Oury F, Tanaka KF, Thomas T, Wang Y, Cremers S, Hen R, Krust A, Chambon P, Karsenty G. Leptin-dependent serotonin control of appetite: temporal specificity, transcriptional regulation, and therapeutic implications. J Exp Med. 2011 Jan 17;208(1):41-52.
  • ≤ 2010

  • Karsenty G, Oury F. The central regulation of bone mass, the first link between bone remodeling and energy metabolism. J Clin Endocrinol Metab. 2010 Nov;95(11):4795-801.
  • Oury F, Yadav VK, Wang Y, Zhou B, Liu XS, Guo XE, Tecott LH, Schutz G, Means AR, Karsenty G. CREB mediates brain serotonin regulation of bone mass through its expression in ventromedial hypothalamic neurons. Genes Dev. 2010 Oct 15;24(20):2330-42.
  • Oury F, Karsenty G. [Serotonin, two faces of a unique molecule in the regulation of bone mass]. Med Sci (Paris). 2010 Aug-Sep;26(8-9):713-8.
  • Shi Y, Oury F, Yadav VK, Wess J, Liu XS, Guo XE, Murshed M, Karsenty G. Signaling through the M(3) muscarinic receptor favors bone mass accrual by decreasing sympathetic activity. Cell Metab. 2010 Mar 3;11(3):231-8.
  • Yadav VK, Oury F, Suda N, Liu ZW, Gao XB, Confavreux C, Klemenhagen KC, Tanaka KF, Gingrich JA, Guo XE, Tecott LH, Mann JJ, Hen R, Horvath TL, Karsenty G. A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell. 2009 Sep 4;138(5):976-89.
  • Oury F, Karsenty G. [Intestinal serotonin and regulation of bone mass]. Med Sci (Paris). 2009 May;25(5):445-6.
  • Matis C, Oury, F, Remacle S, Lampe X, Gofflot F, Picard J.J, Rijli F.M, and Rezsohazy R. Novel target genes for the murne Hoxa2 protein: identification of Lmo1 as part of a Hox dependent regulatory network for hindbrain patterning. Dev Dyn. 2007 Sep 8; 236(9) :2675-84.
  • Oury F, Rijli FM. [Hoxa2: a key gene for the facial somatosensory map]. Med Sci (Paris). 2007 Mar;23(3):247-9.
  • Oury F*, Murakami, Y*, Renaud, JS, Pasqualetti, M, Charnay, P, Ren, SY, and Rijli, FM. Hoxa2- and Rhombomere-Dependent Development of the Mouse Facial Somatosensory Map. Science 2006 Sep 8; 313(5792):1408-13.
  • Permanent researcher
    Anne-Sophie Armand
    -
    +33 (0)1 40 61 53 58
    Alexandre Chamouni
    -
    +33 (0)1 40 61 53 56
    Michel Leibovici
    Researcher
    +33 (0)1 40 61 53 77
    Franck Oury
    -
    +33 (0)1 40 61 53 55
    Permanent engineer
    Valérie Boitez
    -
    +33 (0)1 40 61 53 57
    François Mailliet
    Engineer
    +33 (0)1 40 61 53 58
    Non permanent engineer
    Léa Vinel
    Assistant in Biological Techniques
    Post-doctoral degree
    Miranda Bueno Arribas
    Post-Doctoral Researcher
    David Romeo Guitart
    Post-Doctoral Researcher
    +33 (0)1 40 61 53 56
    PhD
    Victoria Blanchet
    PhD Student
    Mathieu Galerne
    PhD Student
    +33 (0)1 40 61 53 57
    Haiyuxin Zhu
    PhD Student
    Student
    Elodie Cazottes
    -
    Tala Tirani
    -
    Address

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    Support(s)
    HRH Princess Caroline of Hanover, who through the Princess Grace Foundation, already supports medical research and anything that helps to relieve the sick children in France and around the world, has agreed to commit to our side so that our Center of Molecular medicine continues to meet the current challenges and fight diseases, and in particular the ones affecting children.

    INEM - Organigramme