How to Generate New Neurons in the 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 (NSCs) are responsible for building the brain during embryonic development, generating all the cells of the central nervous system, including neurons.

Some areas of the adult brain contain quiescent, or dormant, neural stem cells that can potentially be reactivated to form new neurons. However, the transition from quiescence to proliferation is still poorly understood. 

Surprisingly, NSCs persist in certain brain regions even after the brain is fully formed and can make new neurons throughout life. 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. 

In this new study researchers have uncovered a metabolic mechanism by which adult NSCs can emerge from their dormant state and become active.

”We found that mitochondria, the energy-producing organelles within cells, are involved in regulating the level of activation of adult NSCs,” explains Francesco Petrelli, co-first author of the study. 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.

Biologists have blocked MPC activity by using chemical inhibitors or by generating mutant mice for the Mpc1gene. Using these pharmacological and genetic approaches, the scientists were able to activate dormant NSCs and thus generate new neurons in the brains of adult and even aged mice. ”With this work, we show that redirection of metabolic pathways can directly influence the activity state of adult NSCs and consequently the number of new neurons generated,” summarizes Professor Knobloch, co-lead author of the study. 

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.

Sources: 

Francesco Petrelli, Valentina Scandella, Sylvie Montessuit, Nicola Zamboni, Jean-Claude Martinou, Marlen Knobloch. Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cells. Science Advances, 2023; 9 (9) DOI: 10.1126/sciadv.add5220

Université de Genève. “How to generate new neurons in the brain.” ScienceDaily. ScienceDaily, 1 March 2023. <www.sciencedaily.com/releases/2023/03/230301141432.htm>.

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