Research shows that mammals’ brains expend a substantial amount of their energy as ATP (adenosine triphosphate), the molecule that cells use in energy transfer to support various biological functions. While astrocytes may use stored glycogen to offer some protection to neurons temporarily during low blood sugar levels, persistently low glucose can also lead to neurodegeneration.Â
The research conducted at the Max Planck Institute for Multidisciplinary Studies in Germany, along with an array of other institutions across the globe, showed that glial fatty acid metabolism contributes to energy reserve for use by all other cells within the CNS.
When these scientists published their findings in Nature Neuroscience, the study was shown oligodendroglial lipid metabolism could be used in some cases to reserve energy to fight against neurodegeneration through glucose deprivation. On the creation of the paper, said Klaus-Armin Nave, supervising author of the paper, “The main motivation behind the recent work was a rather speculative idea that myelin might have evolved as a highly specialized lipid store.”Â
“It was purported that myelin emergence in evolution coincided with the removal of lipid droplets from axon-associated glial cells. It had been shown that in mutant Drosophila, excess glycolysis products would be converted in the axon to fatty acids shuttled back to wrapping glia and stored as lipid droplets.”
Being such students of both recently published data, Bellen and other researchers have postulated that myelin might be an inner fatty protective layer enveloping the axons (i.e.,nerve fibers) in the vertebrate CNS; and that myelin would have arisen from the functionality of glial cells to ‘package’ lipids and some proteins into membranes able to fold around the axon.Â
Myelin should, therefore, help in signaling between and among cells and maintain the whole energy supply state once designated. Nave explained: “The optic nerve of adult mice was isolated and then put into culture for simple ex vivo experiments.”
“The survival of its glial cell population under conditions where glucose was present or absent in the culture medium was determined. Oligodendrocytes surprisingly tolerated the lack of glucose quite well, but only so long as the bay be first degraded fatty acids from myelin and then generate ATP by oxidizing the breakdown products with the aid of mitochondria.Â
“Further experimental activities have led these researchers to note that energy of lipids for oligodendrocytes is again used to drive spiking of myelinated axons in the optic nerve.
They used mice with specific cell-type mutations to indicate that oligodendroglial peroxisomes, small organelles within oligodendrocytes and myelin, also take part in the turnover of fatty acids. Nave explained how conditional mouse mutants deficient in glucose transporters from adult oligodendrocytes appeared to be in vivo “starvation.” Â
“Nevertheless, the reason not much was made of this when these were alive is that it seems that the immediate access to fatty acids is because the turnover of the normal myelin lipids is, more or less, continuous. However, during the following months, these mice slowly lost their myelin membranes, according to studies performed using electron microscopy. Â
“These findings support the hypothesis that the myelinated brain of adult mammals has a significant reserve of energy to counteract temporary energy shortages.
These results have far-reaching implications concerning the study of starvation-linked disorders related to loss of brain white matter, such as anorexia nervosa. “Nerve-degenerative diseases associated with gradual myelin loss may well reflect this mechanism of metabolizing fatty acids from the myelin sheath,” says Nave.Â
“We now need to determine just how this metabolic energy from fatty acids derived from myelin is provided to the other glial cells and to the axonal compartment, which all seem to benefit from demyelination. Our speculation is that it could be very short fatty acids or ketone bodies.”Â
