Team Philippe MARIN
Neuroproteomics and signalling of brain disorders
Project Serotonin receptors and psychiatric disorders
PRINCIPAL INVESTIGATOR
IGF staff involved
Philippe MARIN
DRCE CNRS
Joël BOCKAERT
PU UM
Tomas DEL OLMO
Post-doc INSERM
Mehdi SEKKSAOUI
Doctorant UM
Linda-Nora MEKKI
IE INSERM
Psychiatric disorders such as major depression and schizophrenia are now one of the major public health problems, affecting more than 400 million and 21 million people worldwide respectively. However, current treatments have significant limitations. Improving treatments for these psychiatric disorders is therefore a major challenge. While alterations in the serotonin system have been characterized in these psychiatric disorders, the precise role of serotonin and its targets remains unclear and requires in-depth study to identify new therapeutic targets.
New therapeutic strategy to prevent cognitive deficits in preclinical models of schizophrenia
New therapeutic strategy to prevent cognitive deficits in preclinical models of schizophrenia
Schizophrenia is a devastating mental disorder of neurodevelopmental origin, which affects ~1% of the population worldwide and represents a major socio-economic burden. It is characterized by a broad pattern of cognitive symptoms, including decreased attention, impaired memory, inaptitude to solve problems and alterations in social cognition. These deficits are poorly controlled by currently available antipsychotics. progress in disease management will likely require shift to novel modes of intervention initiated at an early stage of the disease in high-risk patients. project aims at proposing a novel disease modifier strategy to prevent emergence of cognitive deficits at the adult stage and conversion to schizophrenia in at-risk subjects. This strategy is based on early blockade of 5-HT6 receptor-operated mTOR signaling during adolescence. By combining cutting-edge multidisciplinary approaches, we will characterize the synaptic and molecular mechanisms underlying the regulation of this mTOR signaling pathway by serotonin 5-HT6 receptors.
Mechanisms of antidepressant action of psychedelics
Major depressive disorder (MDD) is one of the most disabling psychiatric disorders in the world. First-line treatments such as selective serotonin reuptake inhibitors (SSRIs) still have many limitations, including resistance to treatment in 30% of patients and a delayed clinical benefit occurring only after several weeks of treatment. It has recently been shown that acute administration of psychedelic agonists of the serotonin 5- HT2A receptor (5-HT2AR), such as LSD (Lysergic Acid Diethylamide) or psilocybin, induce fast antidepressant effects that persist up to 5 weeks after the treatment in patients with MDD. However, mechanisms underlying their antidepressant-like effect remain poorly understood. The aim of our project is to characterize them in mouse preclinical models.
Principales publications
• Seksaaoui M., et al. (2024) Neuropsychopharmacology, doi: 10.1038/s41386-024-01794-6
• Pedzich B., et al. (2022) Neuropsychopharmacology, 47(7):1304-1314
• Prouzeau D., et al. (2022) Curr Psychiatry Rep. doi: 10.1007
• Doucet E.L., et al. (2021) International Journal of Molecular Sciences, 22:10178.
• Berthoux C. et al. (2020) EMBO Molecular Medecine, doi.org/10.15252/emmm.201910605
• Berthoux C. et al. (2019) Cerebral Cortex, 29(4):1659-1669
• Bécamel C., et al. (2017) ACS Chem Neurosci., 8(5):897-899
• Barre A. et al. (2016) Proc Natl Acad Sci U S A. 2016, 113(10): E1382-91
Financements
• 2023-2025 Polish National Science Centre – Responsable de tâche
• 2020-2025 ANR 2019-NANO4SCHIZO – Responsable de tâche
• 2017-2023 ANR 2016-STOPSERO6TOR – Responsable scientifique
• 2014-2017 FRM Urgence de la Recherche (Physiopathologie de l’Addiction) – Responsable scientifique
Collaborations
• Alain Gardier (Paris)
• Pierre-Jean Corringer (Paris)
• Lucie Berkovitch (Paris)
• Pawel Zajdel (Pologne)
• Dimitri De Bundel (Belgique)
• Philippe Rondard (Montpellier)
• Guillaume Lebon (Montpellier)
• Freddy Jeanneteau (Montpellier)
Alumni
• Angelina Rogliardo (Thèse, 2017-2021)
• Emilie Doucet (Post-doc, 2016-2020)
• Coralie Berthoux (Thèse, 2013-2017)
• Al Mahdi Hamieh (Post-doc, 2015-2016)
• Alexander Barre (Thèse, 2009-2013)
