The goal of the research team is to analyze the roles played by environmental and genetic factors, as well as the interactions between these components, in the etiology and treatment of psychiatric disorders such as depression, anxiety and addiction. The main objective of the team is to identify cellular and molecular mechanisms underlying these pathologies which are associated with major dysfunctions of the monoamine and HPA systems and characterized by cellular plasticity alterations of different brain areas and in particular the hippocampus.
The current research is focused on i) the involvement of 5-HT in the genesis of anxiety-related disorders, ii) the role of neuroplasticity in depressive-like and addiction disorders, and iii) the epigenetic mechanisms associated with gene regulation in rodent depression-like models and addiction.
We are currently working on the following programs:
1/ BDNF/TkB signalling in mood disorders: this research aims at exploring the role of BDNF signaling and its downstream epigenetic regulations in the pathophysiology and treatment of mood disorders. The project is part of a program whose objectives are to characterize novel specific agonists and antagonists with high affinity for TrkB receptor. Their functional properties are characterized in validated in vitro and in vivo assays, and used as novel pharmacological tools for investigating the implications of TrkB in depression-like behaviour in validated animal models.
2/ Serotonin and stress axis in mood disorders: How these two main actors of emotional behaviour are impacting the pathophysiology of anxio-depressive disorders? This project analyzes the effects of different types of stress (chronic mild stress, social defeat stress) on behaviour, neuroplasticity markers (using magnetic resonance spectroscopy and molecular analysis at BDNF/TrkB levels) and dendritic remodelling in the hippocampus of different mouse lines.
3/ PTSD and brain plasticity: PTSD is an anxiety disorder related to exposure to a severe psychological trauma. We are developing an integrative approach to explore the role and the potential therapeutic interest of the BDNF/TrkB pathway in psychiatric traumas. To this aim, mice (with Val/Met human polymorphism as well as 5-HT2CVGV mice) are studied as a model of genetic predisposition to PTSD using innate or conditioning fear. In addition to fear conditioning, we are assessing memory performances in absence of fear components, spatial memory, and 5- CSRTT to evaluate other forms of visual memory and other executive-related behaviors (attention, impulsivity and compulsivity).
4/ Ethanol, plasticity and epigenetics: How ethanol, through the regulation of the epigenetic landscape, can modify brain plasticity? This research is based on the effect of free ethanol intake in different mouse lines (inbred or mutated lines) and used behavioural (fear conditioning), electrophysiological (LTP, LTD), and molecular and epigenetics approaches.