New insights into how neurons metabolize glucose and how this affects the development of brain problems
The human brain uses up nearly a quarter of all the sugar energy in the body, every day. New research has shed light on how neurons consume and metabolize glucose and how these cells adapt to deficiency. Previously, several scientists argued that neurons themselves do not metabolize sugar and that glial cells consume most of the glucose and then indirectly feed the neurons by passing them a metabolic product of glucose called lactate. However, evidence to support this theory has been scant. The new study solved this problem by using induced pluripotent stem cells (iPS cells) to generate human neurons. The experiments revealed that the neurons themselves were able to take up glucose and transform it into smaller metabolites. To determine exactly how neurons used metabolized glucose products, the team removed two key proteins from cells using gene editing CRISPR. One of these proteins enables neurons to import glucose, while the other is required for glycolysis, the primary pathway by which cells metabolize glucose. Removing one of these proteins blocked the breakdown of glucose in human neurons recreated in vitro (in the laboratory) with stem cells. Nakamura’s group then turned to mice to study the importance of neuronal glucose metabolism in live animals. They modified the animals’ neurons to deprive them of proteins necessary for glucose import and glycolysis. As a result, the mice developed severe learning and memory problems as they aged. These new discoveries could lead to the discovery of new therapeutic approaches for neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Additionally, the research provides a deeper understanding of how glucose is used by the brain and could contribute to a better understanding of how to keep the brain healthy as we age.
