The new findings may help in the discovery of new therapies for diseases like Parkinson's disease and Alzheimer's, and help doctors understand how to keep the brain healthy as it ages.
The human brain uses nearly one quarter of the body's sugar energy, or glucose, every day — and now researchers have found new facts on how the neurons metabolise glucose and adapt to its shortage. The new findings can possibly aid in the discovery of more therapeutic approaches for diseases and help doctors understand how to keep the brain healthy as it ages.
Experts at Gladstone Institutes and University of California San Francisco (UCSF) in the United States have detailed the precise process by which neurons that transmit electrical impulses in the brain, use and process glucose through new research methods and tests.
It is known that in the early stages of neurodegenerative ailments, like Parkinson's disease and Alzheimer's, the brain's ability to absorb glucose reduces.
Thus, the latest discoveries may help in the discovery of new therapeutic methods for these illnesses.
Several foods that we eat are broken down into glucose, which is stored in the liver and muscles. The glucose is then transferred throughout the body and metabolised by cells to power the chemical reactions that keep us alive.
Earlier, it was known that a significant portion of glucose was metabolised by additional brain cells known as glia, which facilitate the functioning of neurons. It was understood that these cells fuel neurons indirectly by providing them a metabolic product of glucose called lactate.
"Although we were previously aware of the brain's high glucose demands, the extent to which neurons depend on glucose and the mechanisms they use to metabolise it remained unclear," stated Ken Nakamura, MD, PhD, Associate Investigator at Gladstone and senior author of the recently published study.
With the results of the study, the understanding of glucose and its use by neurons has significantly improved, Nakamura claimed in the official release.
The team of researchers used induced pluripotent stem cells (iPS cells) in order to generate pure human neurons.
Then, the researchers mixed the neurons with a labelled form of glucose, which proved the ability of neurons to take up the glucose themselves and process it.
To pinpoint the method, the team used CRISPR gene editing to remove two essential proteins from the cells. They found that when either of these proteins was removed, the breakdown of glucose in the neurons stopped.
"This is the most direct and clearest evidence, yet those neurons are metabolising glucose through glycolysis and that they need this fuel to maintain normal energy levels," said Nakamura.
The team then used engineered neurons in mice to be low in these proteins. In the study as the mice aged, they experienced severe learning and memory issues suggesting that neurons rely on glycolysis for normal functioning.
The researchers also observed how the neurons adapted themselves in the absence of glucose. They found that neurons used other energy sources, such as the related sugar molecule galactose, which was not as efficient a source of energy as glucose.