特別講演
Plenary Lecture |
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| 2020/9/11 17:40～18:40 Zoom A
PL
Novel functions of myelin in axonal energy metabolism
*Nave Klaus-Armin1、Asadollahi Ebrahim1
1. Max Planck Institute of Experimental Medicine, Germany
*Klaus-Armin Nave1, Ebrahim Asadollahi1
1. Max Planck Institute of Experimental Medicine, Germany
It is well known that myelin enables fast impulse conduction (Cohen et al., 2020). Recently, we identified a new function of oligodendrocytes in providing lactate as metabolic support for the generation of ATP in rapidly spiking axons (Fünfschilling et al., 2012; Trevisiol et al., 2017). Underlying is aerobic glycolysis in the oligodendroglial compartment, which is regulated by NMDA-type glutamate receptors on myelin and the translocation of glucose transporters (GLUT1), upon release of trace amounts of glutamate by spiking axons. Thus, oligodendrocytes can increase the glycolytic flux as a function of axonal spiking frequency and therefore the underlying axonal energy demands (Saab et al., 2016). We have additional unpublished evidence that under starvation conditions myelin itself, which is a highly lipid rich compartment, contributes to the white matter energy balance. In the myelinated optic nerve oligodendrocytes survive glucose deprivation ex vivo for up to 24 hours and much better than astrocytes. Importantly, this survival depends on fatty acid beta-oxidation and involves peroxisomes that reside in the myelin compartment. Fatty acid metabolization also supports axonal ATP levels and conduction properties under low glucose conditions. In vivo, loss of glucose transporter GLUT1 from mature oligodendrocytes causes a slowly progressive loss of myelin (Asadollahi et al., in prep). This suggests a novel working hypothesis for white matter function, in which myelin itself constituting an energy buffer that can prevent axonal degeneration under metabolic stress. These findings may be relevant for a range of neurodegenerative diseases.
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