Sweet insight into memory loss
Glucose might block new neurons from forming

What if forgetfulness didn’t have to be a part of aging?
Our brains become less adept at making new neurons as we age, which gets in the way of holding onto memories and has devastating consequences for people with degenerative brain diseases and brain injuries. Now, discoveries about the impact of glucose in mouse brains suggest routes for eliciting new neuron growth in old brains.
In research published in October 2024 in Nature, Anne Brunet, PhD, professor of genetics, and her team conducted a genomewide search for genes that, when disabled, increase the activation of neural stem cells in brain tissue samples from old mice but not in samples from young ones. Activated neural stem cells “wake up” and start developing into the mature cells like neurons that make up the nervous system.
Of the 300 genes they found that interfered with neural stem cell activation in old mice, one stood out, said Brunet, the study’s senior author. “It was the gene for the glucose transporter protein known as GLUT4, suggesting that elevated glucose levels in and around old neural stem cells could be keeping those cells inactive.”
“The next step,” Brunet continued, “is to look more closely at what glucose restriction, as opposed to knocking out genes for glucose transport, does in living animals.”
Anne Brunet, PhD
Zeroing in on the brain’s hippocampus and the olfactory bulb, where neuron death and replacement are frequent, Tyson Ruetz, PhD, a former postdoctoral scholar in Brunet’s lab and lead author, tested newly identified genetic pathways in old mice. “In these more dynamic parts of the brain, at least in young and healthy brains,” he said, “new neurons are constantly being born and the more transient neurons are replaced by new ones.”
The researchers knocked out the glucose transporter gene in the mouse brain’s subventricular zone, where neural stem cells are activated. Several weeks later, they analyzed the olfactory bulb, the brain region to which new cells migrate from the subventricular zone. They found many new neurons there, proving the technique had a rapid multiplication effect on neural stem cells and significantly increased new neuron production.
Brunet called the glucose transporter connection a hopeful finding not only for pharmaceutical or genetic therapy solutions but also for interventions such as a low carbohydrate diet.
“The next step,” Brunet continued, “is to look more closely at what glucose restriction, as opposed to knocking out genes for glucose transport, does in living animals.”
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