summary: After discovering the importance of cell metabolism in neurogenesis, researchers were able to increase the number of neurons in adult and aged mouse brains.
sauce: University of Geneva
Some regions of the adult brain contain dormant neural stem cells that can be reactivated to form new neurons. However, the transition from quiescence to proliferation is still poorly understood.
A team led by scientists from the Universities of Geneva (UNIGE) and Lausanne (UNIL) discovered the importance of cellular metabolism in this process and identified ways to awaken and reactivate these neural stem cells.
Biologists have successfully increased the number of new neurons in the brains of adult and even older mice.
These promising results for the treatment of neurodegenerative diseases will be found in a journal scientific progress.
Stem cells have the unique ability to continuously generate copies of themselves, giving rise to differentiated cells with more specialized functions. Neural stem cells (NSCs) are responsible for building the brain during embryonic development, generating all the cells of the central nervous system, including neurons.
Neurogenic capacity declines with aging
Surprisingly, NSCs can remain in certain brain regions even after the brain is fully formed and can make new neurons throughout life. important for certain functions such as However, in the adult brain, these stem cells become more silent or ‘dormant’ and less capable of regeneration and differentiation.
As a result, neurogenesis decreases significantly with age.
The labs of Jean-Claude Martinou, Professor Emeritus, Department of Molecular and Cellular Biology, UNIGE Faculty of Science, and Marlen Knobloch, Associate Professor, Department of Biomedical Sciences, UNIL Faculty of Biology and Medicine, discovered metabolism. Mechanisms in which adult her NSCs emerge from dormancy and become active.
“We found that mitochondria, the energy-producing organelles within the cell, are involved in regulating the activation level of adult NSCs,” said UNIL Research Fellow and co-author of the study with Valentina Scandella. Co-lead author Francesco Petrelli explains.
The mitochondrial pyruvate transporter (MPC), a protein complex discovered 11 years ago by Professor Martinu’s group, plays a specific role in this regulation. Its activity influences the metabolic options available to cells.
Knowing the metabolic pathways that distinguish active and dormant cells allows scientists to awaken dormant cells by altering mitochondrial metabolism.
new perspective
Biologists have blocked MPC activity by using chemical inhibitors or by generating mutant mice. Mpc1gene. Using these pharmacological and genetic approaches, scientists were able to activate dormant her NSCs to generate new neurons in the brains of adult and aged mice.
“This study shows that redirection of metabolic pathways can directly affect the activity state of adult NSCs and, consequently, the number of new neurons generated,” said Dr. Co-lead author Professor Knobloch summarizes:
“These results shed new light on the role of cellular metabolism in regulating neurogenesis. Long-term, these results lead to potential treatments for conditions such as depression and neurodegenerative diseases.” It’s possible,” concludes Jean-Claude Martinou, the study’s co-first author.
See also
About this neurogenesis research news
author: Antoine Gueno
sauce: University of Geneva
contact: Antoine Guenot – University of Geneva
image: Images credited to Knobloch Lab – UNIL
Original research: open access.
“Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cells” by Jean-Claude Martinu et al. scientific progress
overview
Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cells
Cellular metabolism is important for adult neural stem/progenitor cell (NSPC) behavior. However, its role in the transition from quiescence to proliferation is not fully understood.
Here, we show that the mitochondrial pyruvate carrier (MPC) plays an important and unexpected role in this process. MPC transports pyruvate to mitochondria, coupling cytosolic glycolysis to the mitochondrial tricarboxylic acid cycle and oxidative phosphorylation. Despite its important metabolic function, the role of MPC in NSPC remains to be resolved.
We show that quiescent NSPCs have active mitochondrial metabolism and express high levels of MPCs. Pharmacological MPC inhibition increases aspartate and causes NSPC activation.
more genetically Mpc1 Ablation in vitro and in vivo also activates NSPCs to differentiate into mature neurons and globally increases hippocampal neurogenesis in adult and aged mice.
These findings highlight the metabolic importance of NSPC regulation and identify a key pathway by which mitochondrial pyruvate import controls NSPC quiescence and activation.
