Objective In the human brain, the 'bottleneck' of neuronal integrity are long axonal projections, which are often the first to degenerate in neuro-psychiatric diseases. We have discovered in mice that oligodendrocytes and Schwann cells are not only essential for the formation of myelin, but also for the functional integrity of axons and their long-term survival. However, the underlying molecular mechanisms have remained obscure. We propose to use experimental mouse genetics to study neuron-glia interactions and to identify axonal signals that control the normal behaviour of myelinating oligodendrocytes. We will then test our hypothesis that axons require oligodendrocytes not only for myelination, but also for the metabolic support of impulse propagation and fast axonal transport. Based on striking pilot observations, we will analyze the mechanisms by which ensheathing glial cells respond to axonal distress and ask in vivo whether they provide glycolysis end products to axonal mitochondria for energy production ('lactate shuttle'). We will also investigate whether myelin lipids are a readily accessible energy store in glia and explore a speculative hypothesis that N-acetyl aspartate is an aspartate-based shuttle of acetyl-CoA residues. If this proposal is successful, we will begin to understand the true function of oligodendrocytes in endogenous neuroprotection and as bystanders of neuronal disease and normal brain aging. This would initiate a paradigm shift for the role of myelinating glial cells, and could open the door for novel therapeutic strategies in a broad range of neurodegenerative diseases, which pose a major burden on the EC health care system. Fields of science natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencesgeneticsnatural sciencesbiological sciencesbiochemistrybiomoleculeslipids Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS5 - ERC Advanced Grant - Neurosciences and neural disorders Call for proposal ERC-2010-AdG_20100317 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV EU contribution € 2 477 800,00 Address HOFGARTENSTRASSE 8 80539 Munchen Germany See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Principal investigator Klaus-Armin Nave (Prof.) Administrative Contact Klaus-Armin Nave (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Germany EU contribution € 2 477 800,00 Address HOFGARTENSTRASSE 8 80539 Munchen See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Principal investigator Klaus-Armin Nave (Prof.) Administrative Contact Klaus-Armin Nave (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
