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The role of myelinating glia in preserving axon function

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.

Field of science

  • /natural sciences/biological sciences/neurobiology

Call for proposal

ERC-2010-AdG_20100317
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Funding Scheme

ERC-AG - ERC Advanced Grant

Host institution

Klinik Max Planck Institut für Psychiatrie
Address
Hofgartenstrasse 8
80539 Muenchen
Germany
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
EU contribution
€ 2 477 800
Principal investigator
Klaus-Armin Nave (Prof.)
Administrative Contact
Klaus-Armin Nave (Prof.)

Beneficiaries (1)

Klinik Max Planck Institut für Psychiatrie
Germany
EU contribution
€ 2 477 800
Address
Hofgartenstrasse 8
80539 Muenchen
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Principal investigator
Klaus-Armin Nave (Prof.)
Administrative Contact
Klaus-Armin Nave (Prof.)