Research suggests that myelin’s fatty acid metabolism may serve as an energy store for the central nervous system

The mammalian brain expends a significant amount of energy in the form of adenosine triphosphate (ATP). It is the molecule that cells use to transfer energy, thereby powering several biological processes.

Unlike other organs with fat cells, neurons and other cells of the central nervous system (CNS) have so far no obvious local energy reserves. While astrocytes can use stored glycogen to temporarily protect neurons during low blood sugar (hypoglycemia), persistent lack of glucose has been shown to contribute to long-term neurodegeneration.

Researchers from the Max Planck Institute for Multidisciplinary Studies in Germany and other institutes around the world recently conducted a study on the contribution of glial fatty acid metabolism to energy storage that can also be used by humans. other cells of the CNS.

Their findings, published in Natural neurosciencesuggest that oligodendroglial lipid metabolism may serve as an energy reserve, thereby helping to overcome glucose deficiency and associated neurodegeneration.

“The main motivation behind our recent paper was a very speculative idea that myelin might have evolved as a highly specialized lipid store,” said Klaus-Armin Nave, supervising author of the paper.

“We proposed that during evolution, the emergence of myelin coincided with the loss of lipid droplets in glial cells associated with axons. Hugo Bellen had demonstrated in mutant Drosophila that an excess of glycolysis products would be converted in the axon into fatty acids which are returned to the glia packaging and stored in the form of lipid droplets.

Based on findings previously collected by Bellen and other researchers, Nave and colleagues hypothesized that myelin, a protective fatty layer that surrounds axons (i.e., nerve fibers) in the Vertebrate CNS, could have evolved as glia learned to “package” stored lipids. and specific proteins in membranes that can be wrapped around axons. As a result, myelin could not only facilitate the transmission of signals between cells, but also maintain its original role as an energy reserve.

“We first performed simple ex vivo experiments by isolating the optic nerve from adult mice and placing it in culture,” Nave explained.

“The survival of its glial cell population was measured in the absence or presence of glucose in the culture medium. The lack of glucose was surprisingly well tolerated by the oligodendrocytes, but only if they could degrade the fatty acids of myelin and generate ATP by oxidizing the breakdown products in the mitochondria.

By conducting further experiments, the researchers found that the energy generated by oligodendrocytes from lipids could also support the electrical spiking activity of myelinated axons in the optic nerve. Using cell-specific mouse mutants, they showed that oligodendroglial peroxisomes, small organelles found in oligodendrocytes and myelin, also play a role in fatty acid turnover.

“When conditional mouse mutants were deprived of glucose transporters from adult oligodendrocytes, these cells were ‘starved’ in vivo,” Nave said. “However, this was tolerated because these myelinating cells have immediate access to fatty acids as normal myelin lipid turnover continues. However, when analyzed by electron microscopy, these mice gradually lost their membranes of myelin.”

The results gathered by Nave and colleagues suggest that the myelinated brain of adult mammals may possess a significant energy reserve that could help temporarily compensate for energy shortages. These findings could have important implications for the study of disorders associated with loss of brain white matter following starvation, such as anorexia nervosa.

“Neurodegenerative diseases associated with progressive loss of myelin may also reflect this mechanism of metabolizing fatty acids from the myelin sheath,” added Nave.

“We now need to determine how exactly the metabolic energy from myelin-derived fatty acids reaches other glial cells and the axonal compartment, all of which appear to benefit from demyelination. We think it might be fatty acids very short or ketone bodies.”

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