They discover how to make new neurons generate in an adult brain

Stem cells have the unique ability to continuously produce copies of themselves and give rise to differentiated cells with more specialized functions. Neural stem cells are responsible for building the brain during embryonic development, generating all the cells of the central nervous system, including neurons.

There are neural stem cells that persist in certain brain regions even after the brain is fully formed. These stem cells are capable of making new neurons throughout their lives. 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 consequence, neurogenesis decreases significantly as a person ages.

The laboratory of Jean-Claude Martinou, from the University of Geneva (UNIGE) in Switzerland, and that of Marlen Knobloch, from the University of Lausanne (UNIL) in Switzerland, have discovered a metabolic mechanism by which adult neural stem cells can come out of their latent state and become active. The team, which includes Francesco Petrelli and Valentina Scandella from UNIL, has also figured out how to get this process going.

The researchers discovered that mitochondria, which are the energy-producing organelles within cells, are involved in regulating the level of activation of adult neural stem cells. The mitochondrial pyruvate transporter, 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 that a cell can use. By understanding the metabolic pathways that distinguish active from inactive cells, scientists can wake up sleeping cells by modifying their mitochondrial metabolism.

Newly produced neurons (red) in the dentate gyrus with cell nuclei (blue) and a marker of immature neurons (green). (Photo: © Knobloch Lab – UNIL)

The study authors blocked the activity of the mitochondrial pyruvate transporter using chemical inhibitors or by generating mice with a mutation affecting the Mpc1 gene. Thanks to these strategies, the scientists were able to activate latent neural stem cells, thereby generating new neurons in the brains of adult or even senile mice.

These results are promising for the treatment of neurodegenerative diseases in humans.

The study is titled “Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cells”. And it has been published in the academic journal Science Advances. (Fountain: NCYT by Amazings)