0
0
In a groundbreaking study, researchers from Duke-NUS Medical School and the Mechanobiology Institute (MBI) at the National University of Singapore (NUS) have identified a critical brain pathway that could pave the way for innovative treatments for neurodevelopmental disorders such as autism, cerebral palsy, and learning disabilities. This research sheds light on the mechanisms that activate dormant neural stem cells in the adult mammalian brain, offering new hope for brain repair and growth.
The study reveals that in the adult brain, most neural stem cells remain in a dormant state until triggered by specific signals. When activated, these stem cells generate new neurons, which are essential for brain repair and regeneration. Disruptions in this activation process have been linked to cognitive decline and neurodevelopmental disorders, including microcephaly.
Neurodevelopmental disorders affect approximately 5% of children and adolescents worldwide, impacting their cognitive, communicative, and motor skills. To investigate how dormant neural stem cells are activated, the researchers used Drosophila, or fruit flies, as their model organism. Much like mammals, fruit flies’ neural stem cells remain inactive until specific signals stimulate them.
The research team made a significant discovery regarding the role of astrocytes—glial cells traditionally known for their supportive functions—in the reactivation of dormant neural stem cells. Using super-resolution microscopy with 10 times magnification, the researchers examined the fine fiber structures of these dormant cells. They identified protrusions about 1.5 micrometers in diameter, rich in actin filaments and regulated by a specific type of formin protein. Variations in formin levels have been associated with neurodevelopmental disorders such as microcephaly, highlighting the importance of this pathway.
The study found that astrocytes release a signaling protein known as Folded gastrulation (Fog). This protein initiates a chain reaction that activates the Formin protein pathway, which controls the movement of actin filaments and reactivates neural stem cells. The GPCR receptor in neural stem cells responds to Fog, triggering this activation process. GPCR proteins, crucial to many cellular processes, are also the target of a significant portion of FDA-approved drugs.
Professor Wang Hongyan, the senior author of the study, emphasized that these findings provide a deeper understanding of the mechanisms governing neural stem cell reactivation. The discovery of astrocytes as key players in this process opens new avenues for influencing neural stem cell behavior and developing targeted therapies.
The research team is now looking to investigate additional signals from astrocytes that may affect neural stem cell activity and to explore similar mechanisms in human brain development. This pioneering work represents a promising step towards novel treatments for neurodevelopmental disorders, potentially improving the quality of life for millions affected by these conditions.
