Skip to main content
Aller à la page d’accueil de la Commission européenne (s’ouvre dans une nouvelle fenêtre)
français fr
CORDIS - Résultats de la recherche de l’UE
CORDIS
Contenu archivé le 2024-05-28

A new logic to control signalling pathways in the mouse brain: The role of MAPK in emotional behavior

Objectif

Mood disorders represent some of the most common and proliferating health problems worldwide. The present knowledge on the molecular regulation and intracellular signalling mechanisms of anxiety and depression behaviour is incomplete. A better understanding and the development of novel, improved therapeutic treatment would fill a medical need. To study the function of signal transduction pathways in the brain requires control of the activity of a signalling protein in a temporal manner in a selected cell type of the brain. Signalling processes undergo cycles of activation and repression, such that their manipulation into both directions is of experimental interest. This project will focus on the development and application of a new inducible and reversible switch to modulate the activity of signalling molecules at the protein level in the postnatal mouse brain, with the MAP Kinase (MAPK) pathway as a case study. This switch relies on the posttranslational activation of hyperactive or dominant negative protein kinase mutants fused with the ERT2 mutant estrogen receptor ligand binding domain. In mice the ERT2 technology is routinely applied to induce the activity of Cre recombinase but is not yet utilised in vivo to manipulate endogenous proteins. Here, B-Raf kinase provides an excellent starting point since the functionality of mutant B-Raf-ERT2 fusion proteins to activate in vitro MAPK signalling is known. By the use of a dominant negative or hyperactive B-Raf fusion protein the fusion protein technology will be for the first time applied to the inducible enhancement or repression of an endogenous signalling pathway in brain neurons. In these mice MAPK signalling can be manipulated in a cell type specific and temporal manner by a small molecule inducer. In particular, the hypothesis that a transient increase of MAPK signalling in glutamatergic neurons of the pubertal brain, results in increased anxiety and depression-like behavior of adult mice, will be tested.

Champ scientifique (EuroSciVoc)

Programme(s)

Thème(s)

Appel à propositions

FP7-PEOPLE-2009-IEF
Voir d’autres projets de cet appel

Régime de financement

MC-IEF - Intra-European Fellowships (IEF)

Coordinateur

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Contribution de l’UE
€ 162 161,00
Coût total
Aucune donnée