Myelin lipids as metabolic energy reserves in white matter tracts
Speaker:
Klaus-Armin Nave, Ph.D.
Director, Deptartment of Neurogenetics
Max Planck Institute of Experimental Medicine
Abstract
In the central nervous system of vertebrates, oligodendrocytes synthesize myelin, a lipid-rich multilayered membrane sheath that electrically insulates axons for fast impulse propagation. As glycolytic cells, oligodendrocytes provide spiking axons with lactate, a metabolic support function of glia that precedes the evolution of myelin. In non-myelinating species, glial cells harbor “lipid droplets”, an energy source that may have evolved into the lipid-rich myelin compartment of higher vertebrates. We thus hypothesized that myelin itself can be a source of energy that is utilized during a metabolic crisis. Using the myelinated optic nerve as a model system, we found that glucose deprived oligodendrocytes readily metabolize myelin lipids and survive, unlike astrocytes, for 24 hours which depends on fatty acid beta-oxidation. Using ex vivo recordings of the optic nerve and metabolic sensors neuronally expressed in transgenic mice, we found that myelin lipid metabolization even supports ATP levels of the underlying axon. Deleting the glucose transporter (GLUT1) gene from mature oligodendrocytes causes a gradual loss of myelin in vivo, as determined by g-ratio analysis. We suggest that myelin is a lipid based metabolic reserve that can prolong oligodendrocyte survival and axonal integrity upon energy deprivation, a finding relevant for myelin disorders and potentially neurodegenerative diseases.
About the Speaker
Klaus-Armin Nave studied Biology obtained his Ph.D. in Neuroscience from the University of California, San Diego, followed by postdoctoral work at the Salk Institute for Biological Studies. He became an independent research group leader at the Center for Molecular Biology (ZMBH) of the University of Heidelberg, where he was promoted to Full Professor in 1998. In 1999, he was recruited by the Max Planck Society to direct the Department of Neurogenetics at the Max Planck Institute of Experimental Medicine in Goettingen. His current research focusses on mechanisms of neuron-glia signaling, glial support of axonal energy metabolism and function, and models of human neuropsychiatric diseases.