Physiopathologie des troubles de l'humeur : dépression et addiction

Institution

Inserm

Laboratory

UMRS 894

Mots clefs

plasticity
Stress
Depression
serotonine/
alcohol
 

publications

Stragier E, Massart R, Salery M, Hamon M, Geny D, Martin V, Boulle F, Lanfumey L. Ethanol-induced epigenetic regulations at the Bdnf gene in C57BL/6J mice. Neuroscience. 2014 Jun 20;271:56-63. doi: 10.1016/j.neuroscience.2014.04.027. Epub 2014 Apr 26.

Doucet EL, Lanfumey L, et al. (2013) Sustained impairment of alpha2A-adrenergic autoreceptor signaling mediates neurochemical and behavioral sensitization to amphetamine. Biol Psychiatry. 74:90-98

Garcia Garcia Al, Lanfumey L, et al. (2013) Regulation of serotonin (5-HT) function by a VGLUT1 dependent glutamate pathway. Neuropharmacology. 70:190-199

Lanfumey L, et al (2012) Biological rhythms and melatonin in mood disorders and their treatments Pharmacol Ther. 138:176-184 Review

Lanteri C, ?, Lanfumey L, et al.. (2013) Repeated exposure to MDMA triggers long-term plasticity of noradrenergic and serotonergic neurons Mol Psychiatry. 2013 Aug 20.

Martin CBP, .. Lanfumey L, .. et al. (2012) RNA splicing and editing modulation of 5-HT2C receptor function: relevance to anxiety and aggression in VGV mice. Mol Psychiatry. 18:656-665

Molet J,  Lanfumey L. Juvenile ethanol exposure increases rewarding properties of cocaine and morphine in adult DBA/2J mice. Eur Neuropsychopharmacol. 2013 Apr 22.

Fields of research

Neurological and psychiatric diseases

Research Theme

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.