Neurogenesis allows the creation of new neurons in our brain, but this process undergoes changes throughout life and neurodegenerative diseases, such as Alzheimer’s or Parkinson’s, deteriorate it and prevent neuronal regeneration. Now, a team of biologists led by researchers from the universities of Geneva (UNIGE) and Lausanne (UNIL) have discovered that in certain areas of the adult brain there are stem cells that can be reactivated to form new neurons.
Stem cells have a unique ability to continue to make copies of themselves and give rise to differentiated cells with more specialized functions, and neural stem cells (NSCs) neural stem cell) are responsible for brain growth during embryonic development and for generating all the cells of the central nervous system, including neurons.
The authors of the new study have succeeded in increasing the number of new neurons in the brain of adult and elderly mice, findings that open up new possibilities for finding effective treatments against neurodegenerative diseases. The results have been published in the scientific journal Science Advances.
Aging impairs the process of neurogenesis
Neural stem cells remain in certain areas of the brain after the complete formation of this organ and can generate new neurons throughout life, which is known as adult neurogenesis, which is essential for learning and memory. In the adult brain, however, these stem cells are ‘dormant’ or ‘asleep’ and their capacity for renewal and differentiation decreases, so that neurogenesis is progressively reduced as growth occurs. brain aging.
“In the long term, these results could lead to potential treatments for conditions such as depression or neurodegenerative diseases.”
The laboratories of Jean-Claude Martinou, Professor Emeritus in the Department of Molecular and Cellular Biology of the UNIGE Faculty of Sciences, and Marlen Knobloch, Associate Professor in the Department of Biomedical Sciences of the UNIL Faculty of Biology and Medicine, have found a metabolic mechanism by which adult NSCs can leave their dormant state and become active again.
“We discovered that the mitochondria, the energy-producing organelles within cells, participate in regulating the level of activation of adult NSCs”, explained Francesco Petrelli, a UNIL researcher and co-author of the study with Valentina Scandella. The mitochondrial pyruvate transporter (MPC), a protein complex discovered eleven years ago in Professor Martinou’s group, plays a specific role in this regulation, since its activity influences the metabolic options that a cell can use.
Knowing the metabolic pathways that differentiate active cells from quiescent cells allows scientists awakening dormant cells by modifying their mitochondrial metabolism. The team of biologists blocked the activity of MPC using chemical inhibitors or by creating mutant mice for the Mpc1 gene. Using these pharmacological and genetic approaches, they were able to activate latent NSCs and thus generate new neurons in the brain of adult and elderly mice.
“With this work, we demonstrate that the redirection of metabolic pathways can directly influence the activity state of adult NSCs and, consequently, the number of new neurons generated”, highlighted Professor Knobloch, co-lead author of the
job. “These results shed new light on the role of cellular metabolism in the regulation of neurogenesis. In the long term, these results could lead to potential treatments for conditions such as depression or neurodegenerative diseases”, concludes Jean-Claude Martinou, co-lead author of the study.