1. BDNF-TrkB signaling through Erk1/2MAPK phosphorylation mediates the enhancement of fear memory induced by glucocorticoids
- Author
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P.V. Piazza, Françoise Rougé-Pont, A. Y. Le Roux, N Kaouane, J-M Revest, Aline Desmedt, Monique Vallée, Valérie Roullot-Lacarrière, F Tronche, Fernando Kasanetz, Mines Nantes (Mines Nantes), UMR 5228, Centre National de la Recherche Scientifique (CNRS), Institut de Physique du Globe de Paris (IPGP), Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique moléculaire, neurophysiologie et comportement, Expression des Gènes et comportement adaptatifs = Molecular Genetics, Neurophysiology and Behavior (NPS-15), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSERM, Agence Nationale pour la Recherche (ANR), Federation Bordeaux Neurosciences (FBN), University Victor Segalen-Bordeaux2, Conseil Regional d'Aquitaine, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, and Centre National de la Recherche Scientifique (CNRS)-Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-IPG PARIS-Institut national des sciences de l'Univers (INSU - CNRS)
- Subjects
Male ,MESH: Hippocampus ,MESH: Receptors, Glucocorticoid ,[SDV]Life Sciences [q-bio] ,MESH: Fear ,Hippocampus ,MESH: Rats, Sprague-Dawley ,Tropomyosin receptor kinase B ,MESH: Brain-Derived Neurotrophic Factor ,Rats, Sprague-Dawley ,Tissue Culture Techniques ,0302 clinical medicine ,Glucocorticoid receptor ,MESH: Tissue Plasminogen Activator ,MESH: Animals ,MESH: Memory ,Phosphorylation ,Receptor ,ComputingMilieux_MISCELLANEOUS ,0303 health sciences ,tissue plasminogen activator ,contextual fear memory ,glucocorticoids ,MESH: Receptor, trkB ,brain-derived neurotrophic factor ,MESH: Stress, Psychological ,Fear ,Psychiatry and Mental health ,Original Article ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Signal transduction ,Psychology ,MESH: Mice, Transgenic ,MAP Kinase Signaling System ,Transgene ,Mice, Transgenic ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Receptors, Glucocorticoid ,MESH: Mice, Inbred C57BL ,Memory ,Animals ,Receptor, trkB ,MESH: Tissue Culture Techniques ,tropomyosin-related kinase B ,Molecular Biology ,extracellular signal-regulated kinases 1/2 mitogen-activated protein kinase ,030304 developmental biology ,Brain-derived neurotrophic factor ,MESH: Phosphorylation ,MESH: MAP Kinase Signaling System ,[SCCO.NEUR]Cognitive science/Neuroscience ,MESH: Male ,Mice, Inbred C57BL ,Neuroscience ,Stress, Psychological ,030217 neurology & neurosurgery - Abstract
International audience; Activation of glucocorticoid receptors (GR) by glucocorticoid hormones (GC) enhances contextual fear memories through the activation of the Erk1/2(MAPK) signaling pathway. However, the molecular mechanism mediating this effect of GC remains unknown. Here we used complementary molecular and behavioral approaches in mice and rats and in genetically modified mice in which the GR was conditionally deleted (GR(NesCre)). We identified the tPA-BDNF-TrkB signaling pathway as the upstream molecular effectors of GR-mediated phosphorylation of Erk1/2(MAPK) responsible for the enhancement of contextual fear memory. These findings complete our knowledge of the molecular cascade through which GC enhance contextual fear memory and highlight the role of tPA-BDNF-TrkB-Erk1/2(MAPK) signaling pathways as one of the core effectors of stress-related effects of GC.
- Published
- 2014