Biologists have discovered how to awaken and reactivate neural stem cells in adult mice.

Some adult brain areas contain quiescent, or dormant, neural stem cells that can be reactivated to form new neurons. However, the transition from quiescence to proliferation needs to be better comprehended.

A team composed by scientists from the Universities of Geneva (UNIGE) and Lausanne (UNIL) identified the significance of cell metabolism in this process and identified a way to wake up and reactivate neural stem cells. Researchers were able to increase the production of new neurons in the brains of adult and even elderly mice. Scientists are reporting these promising results inScience Advances[1].

It is possible for stem cells to continually replicate themselves and differentiate into different types of cells with specialized functions. In embryonic development, neural stem cells (NSCs) generate all the neurons in the central nervous system.

Surprisingly, NSCs persist in specific brain regions even after fully forming the brain and can make new neurons throughout life. A biological process known as adult neurogenesis plays a crucial role in memory and learning functions.

Adult stem cells, however, become more dormant and less capable of renewal and differentiation in the brain. With age, neurogenesis decreases significantly.

A metabolic pathway by which adult NSCs can awaken from their dormant state and become active has been discovered by Jean-Claude Martinou, Emeritus Professor in the Department of Molecular and Cellular Biology at the UNIGE Faculty of Science, and Marlen Knobloch, Associate Professor in the Department of Biomedical Sciences at the UNIL Faculty of Biology and Medicine. We found that mitochondria, the energy-producing organelles within cells, regulate the activation level of adult NSCs, explains Francesco Petrelli, a UNIL research fellow and co-first author of the study.

An important part of this regulation is played by the mitochondrial pyruvate transporter (MPC), a protein complex identified eleven years ago in Professor Martinous group. The metabolic options a cell can use are determined by its activity. Scientists can wake up dormant cells by changing their mitochondrial metabolism by knowing the metabolic pathways that distinguish active cells from dormant cells.

Chemical inhibitors or mutant mice for the MPC1 gene have been used to block MPC activity. Through pharmacological and genetic approaches, the scientists were able to activate dormant NSCs in the brains of mouse adults and even those that were elderly.

Professor Knobloch, co-lead author of the study, describes the study as demonstrating that redirection of metabolic pathways can substantially influence the activity state of adult NSCs and affect the number of new neurons generated. According to Jean-Claude Martinou, co-lead author of the study, these results could lead to potential treatments for conditions such as depression and neurodegenerative diseases.

[1] https://doi.org/10.1126/sciadv.add5220%5B2%5D https://scitechdaily.com/scientists-discover-how-to-generate-new-neurons-in-the-adult-brain/

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