The Pivotal Role of birth in Maintaining Neural Stem Cells: A Breakthrough Study
Birth,one of the most transformative events in life,has long been recognized for its immediate physiological impacts. However, a groundbreaking study led by Kazunobu Sawamoto, a professor at Nagoya City University and the National Institute for Physiological Sciences, and Koya Kawase, a pediatric doctor at Nagoya City University Hospital, has unveiled its profound role in the maintenance of neural stem cells (NSCs). Published in Science Advances, the research sheds light on how birth influences the fate of these critical cells, offering new insights into brain growth and plasticity.
The Importance of Birth in Neural Stem Cell Maintenance
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The transition from the intrauterine too the extrauterine surroundings triggers meaningful metabolic changes in individuals. Despite its importance, the role of birth in the developmental process has remained poorly understood. In the adult mammalian brain, NSCs are retained in the ventricular-subventricular zone (V-SVZ), where they continue to generate new neurons. Most postnatal NSCs are maintained in a quiescent state, ensuring their long-term survival.
Sawamoto’s team focused on radial glia (RG), the embryonic NSCs, and investigated how birth-associated metabolic changes affect their fate. Using metabolomics and single-cell RNA sequencing,the researchers compared the V-SVZ of full-term and preterm birth mice. They discovered that normal term birth triggers RG to become quiescent, a process involving alterations in glutamine metabolism. this change is driven by increased expression of Glul, a gene encoding an enzyme that converts glutamate to glutamine.
The impact of Preterm Birth on Neurogenesis
The study revealed that preterm birth disrupts this critical cellular process. “To understand the role of birth in the maintenance of quiescent NSCs, we evaluated the effects of preterm birth on postnatal neurogenesis,” Sawamoto explained. The team found that RG in preterm birth mice transiently enter a neurogenic state via mTORC1 signaling. However, this premature activation leads to a depletion of the NSC pool, resulting in decreased neurogenesis at the young-adult stage.
The implications extend beyond mice. Analysis of human autopsy brains showed that preterm birth similarly reduces postnatal neurogenesis in the V-SVZ. “Considering that postnatal neurogenesis plays an vital role in brain development and plasticity in humans, the reduction in postnatal neurogenesis may be a cause of worse neurodevelopmental outcomes in preterm infants,” Kawase noted.
The Role of Glul in NSC Maintenance
To further explore the role of Glul, the researchers generated Glul-knockdown and -overexpression lentiviruses and infected RG in vivo.Their experiments demonstrated that sufficient upregulation of Glul at the appropriate time of birth is crucial for maintaining quiescent NSCs. “We have uncovered the significance of birth in the maintenance of quiescent NSCs. Considering that glutamine metabolism also regulates the functions of tissue stem cells other than NSCs, our findings enhance our understanding of the pivotal role of birth in tissue homeostasis and regenerative capacities,” Sawamoto commented.
Key Findings at a Glance
| Aspect | Full-Term Birth | Preterm Birth |
|———————————|————————————–|————————————|
| RG State | Quiescent | Transiently neurogenic |
| Glul Expression | Increased | Impaired |
| Neurogenesis | Maintained | Decreased |
| NSC Pool | Preserved | Depleted |
Implications for Future Research and Clinical Practice
This study not only highlights the critical role of birth in NSC maintenance but also opens new avenues for understanding the developmental challenges faced by preterm infants. By elucidating the mechanisms underlying NSC quiescence, the research paves the way for potential therapeutic interventions to mitigate the adverse effects of preterm birth on brain development.For more details, read the full study in Science Advances here.
The Pivotal Role of Birth in Maintaining Neural Stem Cells: A Breakthrough Study
introduction
Birth, one of the most transformative events in life, has long been recognized for its immediate physiological impacts. Though,a groundbreaking study led by Kazunobu Sawamoto,a professor at nagoya City University and the National Institute for Physiological sciences,and Koya Kawase,a pediatric doctor at Nagoya City University Hospital,has unveiled its profound role in the maintainance of neural stem cells (NSCs). Published in Science Advances, the research sheds light on how birth influences the fate of these critical cells, offering new insights into brain growth and plasticity.
The Importance of Birth in Neural Stem Cell Maintenance
Editor: What motivated your team to investigate the role of birth in neural stem cell (NSC) maintenance?
Dr. Sawamoto: The transition from the intrauterine to the extrauterine habitat triggers importent metabolic changes. Despite its importance, the specific role of birth in developmental processes has remained poorly understood. In the adult mammalian brain, NSCs are retained in the ventricular-subventricular zone (V-SVZ), where they continue to generate new neurons. Most postnatal NSCs are maintained in a quiescent state, which ensures their long-term survival.We wanted to explore how birth influences this critical process.
The Impact of Preterm birth on Neurogenesis
Editor: How does preterm birth affect neurogenesis, and what does this mean for preterm infants?
Dr. Kawase: Our study revealed that preterm birth disrupts the process of NSC quiescence. In preterm birth mice, radial glia (RG), the embryonic NSCs, transiently enter a neurogenic state via mTORC1 signaling. This premature activation leads to a depletion of the NSC pool, resulting in decreased neurogenesis at the young-adult stage. Analysis of human autopsy brains showed that preterm birth similarly reduces postnatal neurogenesis in the V-SVZ.Postnatal neurogenesis plays a vital role in brain advancement and plasticity in humans, so this reduction may contribute to worse neurodevelopmental outcomes in preterm infants.
The Role of Glul in NSC Maintenance
Editor: Can you elaborate on the role of glul in maintaining quiescent NSCs?
Dr. Sawamoto: Certainly. We discovered that normal term birth triggers RG to become quiescent through alterations in glutamine metabolism. This process is driven by increased expression of Glul, a gene encoding an enzyme that converts glutamate to glutamine. To further explore this, we generated Glul-knockdown and -overexpression lentiviruses and infected RG in vivo. Our experiments demonstrated that sufficient upregulation of Glul at the appropriate time of birth is crucial for maintaining quiescent NSCs. This highlights the pivotal role of birth in tissue homeostasis and regenerative capacities.
Key Findings at a Glance
| Aspect | Full-Term Birth | Preterm Birth |
|---|---|---|
| RG State | Quiescent | Transiently neurogenic |
| Glul Expression | Increased | Impaired |
| Neurogenesis | Maintained | Decreased |
| NSC Pool | Preserved | Depleted |
Implications for future Research and Clinical Practice
Editor: What are the broader implications of this study for future research and clinical practice?
Dr. Kawase: This study not only highlights the critical role of birth in NSC maintenance but also opens new avenues for understanding the developmental challenges faced by preterm infants. by elucidating the mechanisms underlying NSC quiescence, our research paves the way for potential therapeutic interventions to mitigate the adverse effects of preterm birth on brain development. For more details,read the full study in Science Advances here.
Conclusion
This interview underscores the groundbreaking findings of Dr. Sawamoto and Dr. Kawase’s research, revealing the profound role of birth in maintaining neural stem cells. Their work provides critical insights into the mechanisms of neurogenesis and the impact of preterm birth, offering hope for future therapeutic advancements to support brain development in preterm infants.
