PROJECT SUPPORTED BY JPND

     

     

     

Synaptic circuit protection in Alzheimer´s disease (AD) and Huntington´s disease (HD): BDNF/TrkB and Arc signaling as rescue factors

Alzheimer´s (AD) and Huntington´s disease (HD) result from the erroneous communication of neurons at synapses in different brain areas (neocortex, hippocampus, striatum). The protein BDNF regulates synaptic communication under healthy conditions. However, insufficient release of BDNF from neurons and defective BDNF signaling in target neurons contribute to cellular malfunctions in AD and HD. Although they are essential to the development of effective therapies, the underlying molecular mechanisms for deficits in synaptic communication in these diseases are not understood.

CircProt will employ AD and HD mouse models to investigate the synapse communication deficits for both diseases. Using microscopy methods to investigate BDNF trafficking and release, electrophysiological recordings to check for altered synaptic activity, structural analysis of synaptic contact points (spines), analysis of intracellular protein networks, and behavioral analysis of memory dysfunction (AD) and motor/ cognitive deficits (HD), CircProt will disentangle the role of defective BDNF function in both diseases. Dis-eased mice will be treated with drugs that either speed up BDNF release or boost BDNF signaling to investi-gate how drug treatment ameliorates synaptic communication. Computational modeling of neuronal cir-cuits will assist in the quantitative analysis of improved synaptic function in response to treatment. Thus, CircProt will aid the development of effective future therapies for both diseases.

Start Date: April 2016

Duration: 3 years

Coordinator:

Volkmar Lessmann
T: +49 391 6714282
E: lessmann@med.ovgu.de

Project Partners:

• Prof. Volkmar Lessmann: Institute of Physiology, Otto-von-Guericke-University Magdeburg, Germany 
• Prof. Eero Castren: Neuroscience Center, University of Helsinki, Finland 
• Dr. Hélène Marie: IPMC-CNRS UMR7275, Valbonne, France 
• Prof. Clive Bramham: Department of Biomedicine, University of Bergen, Norway 
• Prof. Frédéric Saudou: GIN, INSERM U1216, University Grenoble Alpes, France 
• Prof. Kurt Gottmann: Institute of Neuro- and Sensory Physiology, Heinrich-Heine-University Düsseldorf, Germany 
• Prof. Michele Migliore: National Research Council, Institute of Biophysics, Palermo, Italy 
• Prof. Elena Cattaneo: Department of Biosciences, University of Milano, Italy

CircProt consortium including all PIs and some lab members

Acknowledgements:

This is an EU Joint Programme-Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organisations under the aegis of JPND - www.jpnd.eu.
List of national/regional organisations who are funding project, by country, in alphabetical order -- e.g. France, Agence Nationale de la Recherche; Finland: Academia of Finland; Germany: Federal Registry of Education and Research, Italy: Ministry of Research, Norway: Research Council of Norway.
This project has received funding from the European Union´s Horizon 2020 research and innovation programme under grant agreement No 643417.