Groundbreaking research from Stanford Medicine reveals promising insights into how to rejuvenate neural stem cells and stimulate neurogenesis in older brains. This study sheds light on potential therapies and lifestyle changes that could combat age-related cognitive decline and neurodegenerative diseases. Discover how targeting glucose metabolism and primary cilia could be the key to unlocking the brain’s remarkable capacity for self-renewal. Neuroscience, Regenerative Medicine, Aging
Unlocking Regeneration in the Brain
The human brain, that amazing and complex organ can retain detailed long-term data through the fine structural interconnections of its neurons. When we age, however, our brains no longer excel at making new neurons and this inability can cause functional impairment in cognitive capabilities, memory and even lessen healing when it comes to some brain diseases.
Researchers at Stanford Medicine have released a groundbreaking new study published in the prestigious journal Nature shedding light on novel mechanisms which may be partially responsible for this age-related decrease in neural stem cell activity. This research, led by Dr. Anne Brunet found that in older mice but not in younger mice a genome-wide search for genes whose knock-out increased neural stem cell activation could be carried out using cutting-edge CRISPR technology.
The Link to Glucose Transporters
The researchers focused on one gene in particular: The gene for the protein, or glucose transporter, GLUT4. The researchers theorize that this high glucose environment, then, may be a driving force in maintaining the senescent state of aged neural stem cells. When the team knocked out the glucose transporter genes in the subventricular zone of the brain, where neural stem cells are located and which turns into a large part of the olfactory bulb they found that it produced many more actually new neurons in living mice.
What this means is, in theory,we could target these dormant neural stem cells with pharmaceutical or genetherapies and re-awaken them in the brains of seniors to bring back theircognitive function as well as possibly prevent or treat neurodegenerative diseaseslike Alzheimer’s and Parkinson’s. By reducing glucose uptake in aged neural stem cells, such interventions could spur neurogenesis without the need to directly manipulate genes.
Exploring Additional Pathways
Additionally, they have pinpointed other interesting pathways that could be exploited in order to reawaken neural stem cells. They also identified genes involved in primary cilia, which are key to the transmission and processing of signals from proteins like growth factors and neurotransmitters, as being related to activation of neural stem cells. This not only provides proof of concept for the utility of the team’s approach but also hints at some intriguing crosstalk that might exist between glucose metabolism and primary cilium function in the control of neural stem cell quiescence and function.
In the next set of experiments, the research team continued the work to determine whether restriction of glucose by means other than genetically knocking out the genes for glucose transport, could have similar effects on neural stem cell activation in living animals. The researchers believe that greater clarity in these processes could pave the way for new kinds of therapies and lifestyle interventions to help fight age-related cognitive decline and neurodegenerative disease, revealing just some of the wonderful untapped potential of our aging brains.
