Discovered a new mechanism to activate stem cells in the adult brain

Cajal Institute – News

An international study led by CSIC researchers has discovered a new mechanism that controls the activation of stem cells in the brain and that promotes neurogenesis (generation of new neurons) throughout life. The work, which has been featured on the cover of Cell Reports magazine, shows the importance of understanding the genetic keys that promote adult neurogenesis and opens the door to the design of strategies to activate neural stem cells in situations of neuronal loss, such as neurodegenerative diseases. . ⠀

The birth of new neurons does not end in childhood. In some regions of the brain, new neurons continue to form throughout life. The key lies in neural stem cells, which have the potential to generate new neurons. However, normally these cells lie dormant. That is why the work led by Aixa V. Morales, a researcher at the Cajal Institute of the CSIC, acquires great relevance. It has described some proteins, present in stem cells, essential for the activation of adult neurogenesis.

The group has discovered that the Sox5 and Sox6 proteins are found mainly in hippocampal neural stem cells, responsible for memory and learning. “We have used genetic strategies that allow us to selectively eliminate these proteins from the brain stem cells of adult mice and we have shown that they are essential for the activation of stem cells and for the generation of new hippocampal neurons”, explains Aixa V. Morales. .

In this work, the team, in which the groups of Helena Mira, from the Institute of Biomedicine of Valencia (IBV-CSIC) and that of Carlos Vicario, from the Cajal Institute have also participated, have also observed that mutations prevent mice with environmental enrichment (wider and more novel spaces) can generate new neurons. “In favorable environments, there is a greater activation of stem cells and, therefore, a greater number of neurons are generated. However, the elimination of Sox5 from the brain of these mice represents an obstacle to neurogenesis”, indicates Morales.

Finally, other studies have shown that Sox5 and Sox6 mutations in humans cause rare neurodevelopmental diseases, such as Lamb-Shaffer and Tolchin-Le Caignec syndromes. These cause cognitive deficits and autism spectrum disorders. “This work will allow a better understanding of the important neuronal alterations that are manifested in these diseases”, concludes Morales.

Li, L.*, Medina, C.*, García-Corzo, L., Quiroga, A.C., Calleja, E., Córdoba, C., Zinchuk, V., Muñoz, S., Rodríguez-Martín, P., Ciorraga, M., Colmena, I., Fernández, S., Vicario-Abejón, C., Nicolis S., Lefebvre, V., Mira, H. and Morales, A.V. SoxD genes are required for adult neural stem cell activation. Cell Reports DOI: 10.1016/j.celrep.2022.110313

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