The brain requires large amounts of energy to function. Glucose is the primary fuel for neurons. While the adult brain accounts for 20-25% of glucose consumption, developing brains may require an even higher quantity.

How glucose is processed in the brain, however, has remained unknown. Some have suggested that glucose may be metabolized by supporter glial cells and then exported to neurons.

More recent studies suggest that neurons may be able to process glucose on their own. It has been difficult to determine whether this is the case due to difficulties in isolating neurons from glial cells for study.

Understanding how glucose is metabolized for energy in the brain could pave the way for new treatments for conditions linked to glucose uptake, such as Alzheimers disease (AD) and Parkinsons disease (PD).

Recently, researchers conducted cell and mouse studies to assess how glucose is metabolized by neurons.

They found two proteins that make it possible for neurons to metabolize glucose themselves both in cell cultures and in animal models.

Dr. Charles Munyon, a functional neurosurgeon with Novant Health in Charlotte, North Carolina, who was not involved in the study, told Medical News Today:

These findings appear to settle a long-standing controversy fairly definitively, and the study is elegantly designed. While it is still not clear what proportion of neuronal energy comes from direct glucose metabolism, we can be certain that the answer is not negligible.

The study was published in Cell Reports.

For the study, the researchers used induced pluripotent stem cells (iPSCs) to generate human neurons. They then added the neurons to a labeled form of glucose. In doing so, they found that neurons were able to break down glucose into smaller metabolites.

Next, the researchers removed two key proteins for importing and metabolizing glucose from the neurons using CRISPR gene editing. Removing either of these proteins impaired the breakdown of glucose in the human neurons.

This, noted the researchers, means that human neurons indeed metabolized glucose.

The researchers next wanted to see whether the findings translated to animal models. To do so, they engineered neurons in mice to lack the same two key proteins for glucose import and metabolism.

The mice that lacked one of the proteins showed normal memory and learning at 3 months of age, but at 7 months they showed severe learning and memory deficits. For the other tested protein, while both female and male mice had normal memory at three and seven months old, they noted that femalesbut not malesdeveloped learning and memory loss by 12 months.

The researchers noted that further studies are needed to understand what may explain the sex differences.

Lastly, they investigated how neurons adapt when glucose is not available as an energy source. They found that neurons use other energy sources, such as a related sugar molecule, galactose, which was less efficient than glucose as an energy source for the neurons.

The researchers concluded that neurons metabolize glucose by themselves and that they require glucose metabolism for normal function.

When asked about the studys limitations, Dr. James Rini, a neurologist at Ochsner Health, who was also not involved in the study, told MNT that as the study was conducted in mice and in a lab setting, it remains unclear if the findings apply to humans and real-life settings too.

He added that the method used to measure glucose metabolism may not capture the full picture of how neurons metabolize glucose in the brain.

[Furthermore], the study only looked at one aspect of brain functionhow neurons metabolize glucoseand did not investigate other factors that may contribute to brain function, such as the role of other nutrients or neural signaling pathways, he explained.

MNT also spoke with Dr. Fahmeed Hyder, professor of Biomedical Engineering at Yale School of Medicine, who was not involved in the study, about the studys implications. He noted that the study adds a well-established line of experimental evidence suggesting that neurons metabolize glucose on demand.

When asked about the studys implications, Dr Rini added:

Direct glucose metabolism pathway may be a new target for therapeutic interventions in brain diseases. For example, if researchers can find ways to enhance glucose uptake or utilization by neurons, it may be possible to improve brain function in people with neurological disorders such as AD and PD.

There have been multiple trials already that have suggested this, CTAD 2022 data suggests Januvia may be neuroprotective in AD, he explained.

Dr. Charles Munyon noted, however, that there is no evidence that the findings will impact therapeutics for AD or PD.

While it is true that glucose metabolism decreases in these conditions, this is a secondary effect due to accumulation of amyloid/tau or alpha-synuclein, he said.

In summation, from a basic science standpoint, this is a well-designed study that answered a long-standing question. In terms of how this will likely impact medical treatment, I dont see a significant impact coming at all, he concluded.

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Alzheimer's: Study pinpoints key role of glucose in brain activity - Medical News Today