Effect of agomelatine on memory deficits and hippocampal gene expression induced by chronic social defeat stress in mice.

Martin V1, Allaïli N2, Euvrard M1, Marday T1, Riffaud A1, Franc B1, Mocaër E3, Gabriel C3, Fossati P4, Lehericy S2, Lanfumey L1.

Author information

1  Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Université Paris Descartes, Paris, France.
2  Centre de NeuroImagerie de Recherche - CENIR- Inserm UMR1127- CNRS 7225, Institut Cerveau Moelle - ICM, Sorbonne Universités, UPMC UMR S 1127, Paris, France.
3   Institut de Recherches Internationales Servier, IRIS, Suresnes, France.
4  Social and Affective Neuroscience - SAN Laboratory - Inserm U 1127- CNRS UMR 7225- Institut du Cerveau et de la Moelle- ICM - Sorbonne Universités, UPMC UMR S 1127, Paris, France.


Chronic stress is known to induce not only anxiety and depressive-like phenotypes in mice but also cognitive impairments, for which the action of classical antidepressant compounds remains unsatisfactory. In this context, we investigated the effects of chronic social defeat stress (CSDS) on anxiety-, social- and cognitive-related behaviors, as well as hippocampal Bdnf, synaptic plasticity markers (PSD-95, Synaptophysin, Spinophilin, Synapsin I and MAP-2), and epigenetic modifying enzymes (MYST2, HDAC2, HDAC6, MLL3, KDM5B, DNMT3B, GADD45B) gene expression in C57BL/6J mice. CSDS for 10 days provoked long-lasting anxious-like phenotype in the open field and episodic memory deficits in the novel object recognition test. While total Bdnf mRNA level was unchanged, Bdnf exon IV, MAP-2, HDAC2, HDAC6 and MLL3 gene expression was significantly decreased in the CSDS mouse hippocampus. In CSDS mice treated 3 weeks with 50 mg/kg/d agomelatine, an antidepressant with melatonergic receptor agonist and 5-HT2C receptor antagonist properties, the anxious-like phenotype was not reversed, but the treatment successfully prevented the cognitive impairments and hippocampal gene expression modifications. Altogether, these data evidenced that, in mice, agomelatine was effective in alleviating stress-induced altered cognitive functions, possibly through a mechanism involving BDNF signaling, synaptic plasticity and epigenetic remodeling.

Sci Rep. 2017 Apr 4;8:45907. doi: 10.1038/srep45907.

This part of the website could either be in French or English, depending on the sources of the actualities.

Autres Publications

 09 janvier 2019
In vivo Optogenetic Approach to Study Neuron-Oligodendroglia Interactions in Mouse Pups
 21 décembre 2018
Predictive Modulation of Corticospinal Excitability and Implicit Encoding of Movement Probability in Schizophrenia
 07 novembre 2018
Manual Dexterity and Aging: A Pilot Study Disentangling Sensorimotor From Cognitive Decline
 05 novembre 2018
Burnout in medical students before residency: A systematic review and meta-analysis
 03 octobre 2018
Tobacco Smoking and Psychotic-Like Experiences in a General Population Sample
 18 mai 2018
Memory circuits: CA2
 07 mai 2018
Cortical developmental death: selected to survive or fated to die
 05 avril 2018
Plasma amyloid levels within the Alzheimer’s process and correlations with central biomarkers
 02 mars 2018
Longitudinal Analyses of Blood Transcriptome During Conversion to Psychosis.
 15 février 2018
Mapping molecular assemblies with fluorescence microscopy and object-based spatial statistics
 14 février 2018
A disassembly-driven mechanism explains F-actin-mediated chromosome transport in starfish oocytes
 12 décembre 2017
The dynamics of stress: a longitudinal MRI study of rat brain structure and connectome.
 04 octobre 2017
 20 septembre 2017
Soluble Amyloid Precursor Protein Alpha Interacts with alpha3-Na, K-ATPAse to Induce Axonal Outgrowth but Not Neuroprotection: Evidence for Distinct Mechanisms Underlying these Properties
 19 septembre 2017
Transient increase in sAPPa secretion in response to Ab1e42 oligomers: an attempt of neuronal self-defense?
 11 septembre 2017
Methylomic changes in individuals with psychosis, prenatally exposed to endocrine disrupting compounds: Lessons from diethylstilbestrol.
 01 juin 2017
Targeting demyelination via α-secretases promoting sAPPα release to enhance remyelination in central nervous system
 19 avril 2017
Spastin regulates VAMP7-containing vesicles trafficking in cortical neurons.
 05 avril 2017
Effect of agomelatine on memory deficits and hippocampal gene expression induced by chronic social defeat stress in mice.
 14 mars 2017
Cognitive control deficit in patients with first-episode schizophrenia is associated with complex deviations of early brain development.