Team 4: Epigenetics and Pathophysiology of Neurodevelopmental Disorders

Team leader : Dr. Bruno Gonzalez

Research Activites

Publications

Members

Contacts

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Research activities

Team 4, “Epigenetics and Pathophysiology of Neurodevelopmental Disorders,” focuses on neurovascular dysfunction in the pathophysiology of neonatal brain injuries and the resulting neurodevelopmental disorders (NDDs). The team’s work targets two populations of nerve cells, GABAergic interneurons and oligodendrocytes, for which the perinatal period constitutes a significant window of vulnerability that can be linked to vasculo-associated migration and differentiation processes of these lineages.

Specifically, the research project targets the impact of two environmental disruptors: perinatal hypoxia and in utero alcohol exposure, which alter angiogenesis, endothelial cell activity, and consequently, the spatial and functional integration of nerve cells migrating along microvessels, thus contributing to NDDs.

The team’s main objective is to characterize neurovascular dysfunction using epigenetic, molecular, functional, and behavioral approaches to identify vascular biomarkers of brain injury and improve early diagnosis of children at risk of NDDs to improve patient care. This objective is based on the hypothesis that vascular-derived biomarker candidates, because they are circulating, offer added value compared to factors of neuronal or glial origin, which are more difficult to access. This hypothesis is supported by the identification of several endothelial candidates (PlGF, CD146), one of which has been the subject of economic and clinical valorization.

In terms of structuring positions, the research team is a member of the Biomedical Research and Innovation Institute. It is multidisciplinary, associating physicians and academic researchers, and has marked interaction with the Neonatal Pediatrics Department of the Rouen CHU. It benefits from local technological infrastructures (Genomics Platform (Asgard), Imaging Platform (PRIMACEN), Behavioral Study Platform (SCAC)). The team has established national collaborations (S. Gil (Paris), D. Vivien (Caen), S. Picaud (Paris), P Gressens (Paris)) and international collaborations (D. Savage (Albuquerque, USA), F. Valenzuela (Albuquerque, USA), L. Telley (Lausanne, Switzerland)). It is a member of national networks (GIS Autism and NDD; National Research Network in Alcoholism (REseaU NatIonal de Recherche en Alcoologie); France BioImaging – Normandy node) and international networks (EUFASD; Euro-Bioimaging). As such, the team is a member of the organizing committee for the next international EUFASD 2026 Congress, supported by the patient association “Vivre avec le SAF.”

Team members are highly involved in public scientific outreach, knowledge dissemination at the national and international levels, teaching through Master’s responsibilities, and participation in transversal evaluation and expertise structures.

Flagship publications

Beranger A, Lafenêtre M, Lacomme S, Lebon A, Genty D, Brosolo M, Janin F, Leroy A, Guérout N, Vivien D, Galas L, Marret S, Marguet F, Gontier E, Gonzalez BJ, Lecointre M. Involvement of the Endothelial N-Methyl-d-Aspartate Receptor on Vessel-Associated Positioning and Differentiation of Cortical Oligodendrocytes and on Motor Activity. J Neurosci. 2025, 45:e0199252025.

Dumanoir M, Leroy A, Burel D, Laquerrière A, Janin F, Lebon A, Valet M, Godefroy D, Przegralek L, Lecointre M, Picaud S, Marret S, Marguet F, Gonzalez BJ*, Brasse-Lagnel C*. In Utero Alcohol Exposure Impairs Retinal Angiogenesis and the Microvessel-Associated Positioning of Calretinin Interneurons. eNeuro. 2023, 10:ENEURO.0295-22.2022. doi: 10.1523/ENEURO.0295-22.2022. *equally contributed

Sautreuil C, Lecointre M, Dalmasso J, Lebon A, Leuillier M, Janin F, Lecuyer M, Bekri S, Marret S, Laquerrière A, Brasse-Lagnel C, Gil S, Gonzalez BJ. Expression of placental CD146 is dysregulated by prenatal alcohol exposure and contributes in cortical vasculature development and positioning of vessel-associated oligodendrocytes. Front Cell Neurosci. 2024, 17:1294746.

Sautreuil C, Lecointre M, Derambure C, Brasse-Lagnel C, Leroux P, Laquerrière A, Nicolas G, Gil S, Savage DD, Marret S, Marguet F, Falluel-Morel A*, Gonzalez BJ*. Prenatal Alcohol Exposure Impairs the Placenta-Cortex Transcriptomic Signature, Leading to Dysregulation of Angiogenic Pathways. Int J Mol Sci. 2023, 24:13484. doi: 10.3390/ijms241713484. *equally contributed
Rodriguez-Duboc A, Basille-Dugay M, Debonne A, Rivière MA, Vaudry D, Burel D. Apnea of prematurity induces short and long-term development-related transcriptional changes in the murine cerebellum. Curr Res Neurobiol. 2023, 5:100113. doi: 10.1016/j.crneur.2023.100113.

Marguet F, Brosolo M, Friocourt G, Sauvestre F, Marcorelles P, Lesueur C, Marret S, Gonzalez BJ, Laquerrière A. Oligodendrocyte lineage is severely affected in human alcohol-exposed foetuses. Acta Neuropathol Commun. 2022, 10:74. doi: 10.1186/s40478-022-01378-9.

Brosolo M, Lecointre M, Laquerrière A, Janin F, Genty D, Lebon A, Lesueur C, Vivien D, Marret S, Marguet F, Gonzalez BJ. In utero alcohol exposure impairs vessel-associated positioning and differentiation of oligodendrocytes in the developing neocortex. Neurobiol Dis. 2022, 171:105791. doi: 10.1016/j.nbd.2022.105791.

Leroux S, Rodriguez-Duboc A, Arabo A, Basille-Dugay M, Vaudry D, Burel D. Intermittent hypoxia in a mouse model of apnea of prematurity leads to a retardation of cerebellar development and long-term functional deficits. Cell Biosci. 2022, 12:148.

Legouez L, Le Dieu-Lugon B, Feillet S, Riou G, Yeddou M, Plouchart T, Dourmap N, Le Ray MA, Marret S, Gonzalez BJ, Cleren C. Effects of MgSO4 Alone or Associated with 4-PBA on Behavior and White Matter Integrity in a Mouse Model of Cerebral Palsy: A Sex- and Time-Dependent Study. Int J Mol Sci. 2022, 23:15947. doi: 10.3390/ijms232415947.