John Taylor, Professor of Economics at Stanford University and developer of the "Taylor Rule" for setting interest rates | Stanford University
John Taylor, Professor of Economics at Stanford University and developer of the "Taylor Rule" for setting interest rates | Stanford University
Most neurons in the human brain are preserved for a lifetime, maintaining critical information through complex synaptic relationships. However, some new neurons are produced by neural stem cells even in adulthood. As the brain ages, its ability to generate new neurons diminishes, which can impact memory and contribute to degenerative diseases like Alzheimer's and Parkinson's.
A study from Stanford Medicine, published on October 2 in Nature, explores why neural stem cells become less active with age and suggests ways to potentially stimulate neurogenesis. Anne Brunet, PhD, professor of genetics at Stanford, led the research using CRISPR technology to identify genes that could activate neural stem cells in older mice.
Brunet's team identified 300 genes capable of activating these cells but focused on one gene related to the GLUT4 protein, a glucose transporter. "Elevated glucose levels in and around old neural stem cells could be keeping those cells inactive," said Brunet.
Tyson Ruetz, PhD, lead author of the study and former post-doctoral scholar in Brunet’s lab, developed an in vivo method to test these genetic pathways. By knocking out glucose transporter genes in specific brain regions of mice and observing increased neuron production, they confirmed the gene's role in activating neural stem cells.
Ruetz explained that this approach allowed them to observe key functions: proliferation of neural stem cells, migration to the olfactory bulb, and formation of new neurons. This technique may also aid studies on brain damage repair.
The link between glucose transporters and neuron growth is promising for developing therapies or behavioral interventions like low carbohydrate diets. The researchers also noted other potential pathways involving primary cilia that could offer alternative treatment options.
"There might be interesting crosstalk between the primary cilia – and their ability to influence stem cell quiescence, metabolism, and function – and what we found in terms of glucose metabolism," Brunet said. Future research will explore glucose restriction effects on living animals.
The study received support from the National Institutes of Health, Stanford Brain Rejuvenation Project, and Larry L. Hillblom Foundation Postdoctoral Fellowship.
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