Researchers discover a gene that controls memory

An investigation of Cajal-CSIC Neuroscience Center from Madrid has discovered a new mechanism (The ‘Sox5’ gene) that controls how adult neural stem cells are generated during the development of the dentated turn, a region of the hippocampus involved in memory and learning.

The study, led by the person responsible for the Molecular control laboratory of neurogenesisthe doctor Aixa Morales, It has been carried out in mice and focuses on these neural cells that remain in a state of rest known as quiescence, in which they are not mature cells or are divided to generate neurons, but in which they can be activated when necessary. This “rest” strategy guarantees that they are not exhausted prematurely.

What was not well known until now was what mechanisms they ensure that their entry into quiescence is correct and reversible. Thus, this work shows that the ‘Sox5’ gene is “crucial” for Establish that rest state in a balanced wayaffirm the authors. Previous studies had shown that ‘Sox5’ is important for the adult neurogenesisand, now, this research shows that it is also necessary for formation of neural stem cells themselves during the development of the dentated turn.

On the other hand, the results of the study published in ‘PLOS Biology’ also reveal that the BMP signaling route (Bone Morphogenetic Proteins), key in embryonic development, is overactivated when ‘Sox5’ is missing. The BMP pathway promotes quiescence, and in the absence of ‘Sox5’ it is disregarded and this prevents maintaining the necessary balance between rest and activation of stem cells.

“Inhibiting this route with small molecules that were injected into the mice that lacked ‘Sox5’, it was possible to reverse some of the alterations caused by the loss of this gene in the neural stem cells,” explains the researcher at the Cajal and co -author of the study, Paula Tirado. Thus, this finding opens the door to possible therapeutic strategies aimed at modulating the BMP pathway in neuronal loss contexts, such as aging or neurodegenerative diseases.

Likewise, another of the relevant findings is the identification of a “critical” temporary window during the second week after birth, in which the appropriate balance between two rest states of neural stem cells is established: a deep state that keeps them inactive for long periods, and another superficial, in which they are closer to activate.

During this temporal window, Sox5 limits the entry of neural stem cells at superficial rest; An essential action to avoid transitory overproduction of neurons in youth, which could exhaust the reserve of stem cells, and therefore, reduce the ability to regenerate the brain in adult life, the authors point out.

In addition, in humans, mutations in the sox5 gene are related to the Lamb-Shaffer syndrome, A rare disease that manifests itself with language disorders, cognitive alterations and features of the autistic spectrum. This new work offers a framework to deepen the altered cell mechanisms in these patients and explore treatment approaches in the future, the study points out.

It also shows the importance of unraveling the genetic keys that promote adult neurogenesis during development and opens the door to the design of strategies to activate neural stem cells in situations of neuronal loss as occurs in neurodegenerative diseases, he concludes.