How to generate new neurons in the brain

Date:
March 1, 2023
Source:
Universite' de Gene`ve
Summary:
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. A team has discovered the importance
of cell metabolism in this process and identified how to wake up
these neural stem cells and reactivate them. Biologists succeeded
in increasing the number of new neurons in the brain of adult and
even elderly mice.


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FULL STORY ==========================================================================
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. A team led by scientists from the Universities of Geneva
(UNIGE) and Lausanne (UNIL) has discovered the importance of cell
metabolism in this process and identified how to wake up these neural
stem cells and reactivate them. Biologists succeeded in increasing the
number of new neurons in the brain of adult and even elderly mice. These results, promising for the treatment of neurodegenerative diseases,
are to be discovered in the journal Science Advances.


==========================================================================
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.

Neurogenesis capacity decreases with age 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.The laboratories of 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, 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, research fellow at UNIL and
co-first 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 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.

New perspectives 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.

''These results shed new light on the role of cell 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.

* RELATED_TOPICS
o Health_&_Medicine
# Stem_Cells # Nervous_System # Brain_Tumor #
Immune_System
o Mind_&_Brain
# Neuroscience # Brain_Injury # Intelligence #
Brain-Computer_Interfaces
* RELATED_TERMS
o Adult_stem_cell o Stem_cell o Embryonic_stem_cell o
Neural_network o Chemical_synapse o Neuron o Neurobiology
o Retina

========================================================================== Story Source: Materials provided by Universite'_de_Gene`ve. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. 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 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/03/230301141432.htm

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