have shed new light on exactly how neurons—the cells that send electrical signals through the brain—consume and metabolize glucose, as well as how these cells adapt to glucose shortages.
Scientists have long debated what happens to glucose in the brain, and many have suggested that neurons themselves don’t metabolize the sugar. They instead proposed that glial cells consume most of the glucose and then fuel neurons indirectly by passing them a metabolic product of glucose called lactate. However, the evidence to support this theory has been scant—in part because of how hard it is for scientists to generate cultures of neurons in the lab that do not also contain glial cells.
To determine exactly how neurons were using the products of metabolized glucose, the team removed two key proteins from the cells using CRISPR gene editing. One of the proteins enables neurons to import glucose, and the other is required for glycolysis, the main pathway by which cells typically metabolize glucose. Removing either of these proteins stopped the breakdown of glucose in the isolated human neurons.
Yoshi Sei is the first author of a new study—led by UCSF’s Chaumeil and Gladstone’s Nakamura —that provides the clearest evidence to date that neurons need glucose to maintain normal energy levels. Credit: Michael Short/Gladstone Institutes Finally, Nakamura and his collaborators probed how neurons adapt when they are not able to get energy through glycolysis—as might be the case in certain brain diseases.