Advantage and Core Benefit
- Elucidation of the molecular mechanisms underlying neurodevelopmental abnormalities in preterm infants.
- Potential therapeutic application using rapamycin, an mTOR signaling inhibitor.
- Expected application in the development of nutritional and therapeutic agents to improve the neurodevelopmental prognosis of preterm infants.
Background and Technology
Preterm infants are known to have a higher risk of developmental disorders and psychiatric conditions, but the molecular mechanisms underlying these neurodevelopmental issues remain largely unexplored.
This study used a preterm mouse model to perform metabolomic and single-cell gene expression analyses. In full-term mice, glutaminolysis (conversion of glutamine to α-ketoglutarate (αKG)) in radial glia decreases after birth. However, in preterm mice, this reduction is incomplete, leading to αKG accumulation and mTORC signaling activation. Consequently, radial glia become excessively activated, temporarily increasing neural progenitor cell production but eventually depleting the neural stem cell pool, reducing long-term neurogenesis.
Administering rapamycin, an mTOR signaling inhibitor, to preterm mice successfully suppressed radial glia overactivation, maintained neural stem cells, and normalized neurogenesis. These findings suggest that mTOR signaling regulation could be a promising strategy to improve neurodevelopmental outcomes in preterm infants.
Data
- In preterm mice (■), compared to full-term control mice (□), neural progenitor cells (Mash1-positive cells) temporarily increased after birth but then decreased, leading to reduced production of newborn neurons (Dcx-positive cells) at day 47.5 (A, B).
- In the autopsied brains of human preterm infants, the number of Dcx-positive cells (newborn neurons) was significantly lower compared to full-term infants (C, D).
- Administration of rapamycin, an mTOR signaling inhibitor, to preterm mice on postnatal days 0 and 2 resulted in an increase in neural progenitor cells and improved neurogenesis at day 29 after birth.
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Patent & Publication
Patent application pending
Kawase et al., Sci. Adv. 11, eadn6377 (2025), [DOI]:10.1126/sciadv.adn6377
Researcher
Prof. Kazunobu Sawamoto (Nagoya City University Graduate School of Medical Sciences)
Expectations
Nagoya City University is seeking collaboration with companies interested in jointly developing nutritional products that normalize glutamine metabolism and neurogenesis for preterm infants, as well as therapeutic agents to improve neurodevelopmental outcomes.
We welcome direct meetings with the researchers to discuss potential collaborations.
Project ID:WL-04750