Some areas of the adult brain contain quiescent, or dormant, neural stem cells that can be reactivated to form new neurons. A team of scientists from the Universities of Beneva and Lausanne have discovered the importance of cell metabolism in this process and identified how to wake up these neural stem cells and reactivate them. By increasing the number of new neurons in the brain of adult and elderly mice, these results are promising for treating neurodegenerative diseases. They were published in the journal Science Advances.
Neural stem cells and neurogenesis
Neural stem cells (NSCs) generate all the central nervous system cells, including neurons, during embryonic development. Surprisingly, NSCs persist in certain brain regions even after the brain is fully formed and can make new neurons throughout a person’s lifetime. This biological phenomenon, called adult neurogenesis, is important for specific functions such as learning and memory processes. However, in the adult brain, these stem cells become more silent or ‘‘dormant’’ and reduce their capacity for renewal and differentiation. As a result, neurogenesis decreases significantly with age.
The role of mitochondria in regulating adult neurogenesis
The laboratories of Jean-Claude Martinou and Marlen Knobloch have uncovered a metabolic mechanism by which adult NSCs can emerge from their dormant state and become active. Mitochondria, the energy-producing organelles within cells, are involved in regulating the level of activation of adult NSCs.
The mitochondrial pyruvate transporter (MPC), a protein complex discovered eleven years ago in Professor Martinou’s group, plays a particular role in this regulation. Its activity influences the metabolic options a cell can use. By knowing the metabolic pathways that distinguish active cells from dormant cells, scientists can wake up dormant cells by modifying their mitochondrial metabolism.
Activating dormant NSCs
Scientists have blocked MPC activity by using chemical inhibitors or by “generating mutant mice for the _Mpc1_gene'” These pharmacological and genetic approaches have enabled the scientists to activate dormant NSCs and generate new neurons in the brains of adult and elderly mice.
These results show that redirection of metabolic pathways can directly influence the activity state of adult NSCs and consequently the number of new neurons generated. They shed new light on the role of cell metabolism in the regulation of neurogenesis. In the long term, they could lead to potential treatments for conditions such as depression or neurodegenerative diseases.
