Contributions
Abstract: 981
Type: Oral
Oligodendrocytes are best known for making myelin, which speeds up axonal impuls propagation and is essential for motor-sensory functions. We found that oligodendrocytes are also required for the long-term function and survival of axons in white matter tracts, a function independent of myelin itself. The two functions of oligodendrocytes in myelination and axonal support can even be genetically uncoupled in mouse mutants. MBP-deficient oligodendrocytes fail to myelinate, but they engulf axons that remain fully functional. In contrast, PLP- or CNP-deficient oligodendrocytes myelinate well but cannot fully support axon function, causing Wallerian degeneration and premature death. WE could recently show that oligodendroytes support axon function by supporting their energy metabolism with glucose-derived lactate as a fuel for axonal mitochondria. This supportive function is especially important for myelinated tracts in which the insulating myelin sheaths shield axons from metabolites of the extracellular milieu. Moreover, the generation of lactate must be matched to the real axonal energy needs to prevent lactic acidosis. Spiking axons release glutamate and myelinating oligodendrocytes use NMDA receptors to detect glutamate release as a proxy for average spiking activity and axonal energy needs. The activation of oligodendroglial NMDA receptors causes a rapid redistribution of glucose transporters to the oligodendroglial cell surface, leading to enhanced glucose import and lactate release. In mice lacking oligodendroglial NMDA receptors functional GLUT1 expression in oligodendrocytes is reduced, which perturbs axon function under metabolic stress. Loss of metabolic support by injured oligodendrocytes is likely a contributing factor for axonal degeneration in multiple sclerosis.
Disclosure: nothing to disclose
Abstract: 981
Type: Oral
Oligodendrocytes are best known for making myelin, which speeds up axonal impuls propagation and is essential for motor-sensory functions. We found that oligodendrocytes are also required for the long-term function and survival of axons in white matter tracts, a function independent of myelin itself. The two functions of oligodendrocytes in myelination and axonal support can even be genetically uncoupled in mouse mutants. MBP-deficient oligodendrocytes fail to myelinate, but they engulf axons that remain fully functional. In contrast, PLP- or CNP-deficient oligodendrocytes myelinate well but cannot fully support axon function, causing Wallerian degeneration and premature death. WE could recently show that oligodendroytes support axon function by supporting their energy metabolism with glucose-derived lactate as a fuel for axonal mitochondria. This supportive function is especially important for myelinated tracts in which the insulating myelin sheaths shield axons from metabolites of the extracellular milieu. Moreover, the generation of lactate must be matched to the real axonal energy needs to prevent lactic acidosis. Spiking axons release glutamate and myelinating oligodendrocytes use NMDA receptors to detect glutamate release as a proxy for average spiking activity and axonal energy needs. The activation of oligodendroglial NMDA receptors causes a rapid redistribution of glucose transporters to the oligodendroglial cell surface, leading to enhanced glucose import and lactate release. In mice lacking oligodendroglial NMDA receptors functional GLUT1 expression in oligodendrocytes is reduced, which perturbs axon function under metabolic stress. Loss of metabolic support by injured oligodendrocytes is likely a contributing factor for axonal degeneration in multiple sclerosis.
Disclosure: nothing to disclose