Singapore researchers discover how to activate dormant brain stem cells to treat neurodevelopmental disorders

Medical News: In a groundbreaking development, researchers from Duke-NUS Medical School and the Mechanobiology Institute (MBI) at the National University of Singapore (NUS) have identified a novel method to activate dormant neural stem cells in the brain. This discovery could pave the way for new treatments targeting a range of neurodevelopmental disorders, including autism, learning disabilities, and cerebral palsy. The research covered in this Medical News report, offers fresh insights into brain development and potential therapeutic strategies for neurological conditions that affect millions worldwide.


Singapore researchers discover how to activate dormant brain stem cells to treat
neurodevelopmental disorders

Neurodevelopmental disorders, which impact around five percent of children and adolescents globally, are characterized by impaired cognitive, communicative, and psychomotor abilities. These conditions often arise from defects in the activation of neural stem cells, which play a crucial role in brain repair and growth. The findings from this study could offer a new avenue for addressing these defects, potentially improving the quality of life for those affected by such disorders.
 
The Role of Neural Stem Cells in Brain Development
Neural stem cells are the brain's building blocks, capable of differentiating into various types of brain cells. In the adult mammalian brain, most neural stem cells remain in a dormant state until specific signals trigger their activation. Once activated, these cells can produce new neurons, aiding in brain repair and growth. However, when this activation process is disrupted, it can lead to cognitive decline and neurodevelopmental disorders, such as microcephaly - a condition characterized by an abnormally small head and underdeveloped brain.
 
The research conducted by the Singaporean team focused on understanding the mechanisms behind the activation of these dormant stem cells. By studying the neural stem cells of Drosophila, or fruit flies, which share similarities with mammalian neural stem cells, the researchers uncovered critical insights into the role of certain glial cells, particularly astrocytes, in waking up these dormant cells.
 
Astrocytes: The Unsung Heroes of Brain Function
Astrocytes have traditionally been viewed as supportive cells in the brain, providing structural and nutritional assistance to neurons. However, the Singaporean researchers discovered that astrocytes play a far more active role in brain function than previously thought. Specifically, they found that astrocytes are essential for activating dormant neural stem cells in the brains of fruit flies.

Using advanced super-resolution microscopy, which allowed the scientists to observe cellular structures at ten times the magnification of traditional methods, the team examined the fine fiber structures that characterize dormant neural stem cells. These structures, approximately 1.5 micrometers in diameter, are rich in actin - a protein that forms filaments within the cell. The activation of these f ilaments is controlled by a type of Formin protein, which is crucial for the assembly and function of these cellular structures.
 
The Key Pathway: GPCR Signaling and Actin Filaments
The study revealed that astrocytes release a signaling protein known as Folded gastrulation (Fog), which initiates a cascade of events leading to the activation of dormant neural stem cells. This process involves the activation of the GPCR (G protein-coupled receptor) protein pathway, which controls the movement and organization of actin filaments within the stem cells. These filaments are essential for cellular functions, including the division and differentiation of neural stem cells.
 
GPCRs are a large family of receptor proteins that play significant roles in various cellular processes. Notably, 34 percent of FDA-approved drugs target GPCRs, highlighting their importance in medical research and drug development. The discovery of the role of GPCR signaling in the activation of neural stem cells opens new possibilities for repurposing existing drugs to treat neurodevelopmental disorders.
 
Potential Applications and Future Research
The implications of this research are profound. By understanding how astrocytes influence the behavior of neural stem cells through GPCR signaling, scientists now have a potential new strategy for treating neurodevelopmental disorders. This could involve developing therapies that specifically target the signaling pathways involved in stem cell activation, thereby promoting brain repair and growth in individuals with these conditions.
 
Moreover, this discovery adds a significant piece to the puzzle of brain development, particularly in understanding how defects in stem cell activation contribute to neurological conditions. The researchers at Duke-NUS and MBI are now exploring other signals from astrocytes that may influence neural stem cell activity. They are also investigating whether similar mechanisms are at play in human brain development, which could further enhance the therapeutic potential of their findings.
 
The Broader Impact on Neurological Research
The research conducted by the Singaporean team is part of a broader effort to deepen our understanding of the fundamental mechanisms that govern brain function and development. This knowledge is crucial for developing new treatments for a range of neurological disorders, including those related to aging, brain injury, and neurodegeneration.
 
As Professor Wang Hongyan, Acting Program Director of Duke-NUS' Neuroscience & Behavioral Disorders Research Program, explained, "Our findings add new knowledge to the limited body of research on mechanisms governing the reactivation of dormant neural stem cells. With our discovery of astrocytes as a key player in the reactivation of neural stem cells, we now have a new way to influence neural stem cell behavior."
 
Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, emphasized the potential of this research to advance therapies for neurological disorders, brain aging, and injury. The discovery not only enhances our understanding of brain cell development but also opens up new avenues for developing targeted treatments that could significantly improve patient outcomes.
 
Conclusion: A New Horizon in Neurodevelopmental Disorder Treatment
The discovery of how to activate dormant neural stem cells through the influence of astrocytes marks a significant milestone in neurological research. This breakthrough could lead to the development of novel therapies for neurodevelopmental disorders, offering hope to millions of individuals affected by these conditions.
 
As the researchers continue to explore the mechanisms underlying stem cell activation, the potential for translating these findings into clinical applications becomes increasingly promising. The work done by Duke-NUS Medical School and the Mechanobiology Institute at NUS represents a critical step forward in our quest to understand and treat the complex disorders of the brain.
 
The study findings were published in the peer reviewed journal: Science Advances.
https://www.science.org/doi/10.1126/sciadv.adl4694
 
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