Activating neural stem cells will help the brain recover

Scientists from Kyoto University have discovered two genes, Hes1 and Ascl1, which are responsible for the rest and activity of adult neural stem cells. By controlling the expression of these genes, it is possible to “turn on” sleeping cells for the treatment of many neurological diseases.

The human body has a powerful recovery mechanism. However, the treatment of brain diseases is no easy task, since its cells, neurons, have limited regenerative potential. However, there is a natural reserve of the body that can restore almost any type of tissue – stem cells.

The peculiarity of neural stem cells is that with age, they are mostly at rest and it becomes more and more difficult for them to activate to repair damage. Despite attempts to use these cells to treat neurological injuries, scientists have until recently failed to decipher the underlying mechanism of their “sleep.”

In the new work, researchers from Kyoto University, who study brain chemistry in mice, have discovered the “tides” and “ebb” of gene expression that can activate neural stem cells. The results, also applicable to stem cells in other parts of the body, were published in the journal Genes & Development.

“No one before us has directly compared active stem cells in embryos with inactive, ‘quiescent’ adult stem cells”, – says group leader Ryoichiro Kageyama.

Scientists have concluded that the activation of stem cells is regulated by at least two genes, as well as proteins associated with them.

The team focused on the Hes1 protein, which is actively expressed in mature stem cells. Under natural conditions, this process inhibits the production of other proteins, such as Ascl1, small amounts of which are periodically expressed by active stem cells. Controlling the production of both proteins, scientists eventually found that the activation of stem cells and their subsequent transformation into neurons is wavy.

When the researchers knocked out the gene, necessary for the production of Hes1, the cells began to synthesize more Ascl1, which activated almost all neural stem cells.

“It is key that the same genes are responsible for both the active and quiescent states of these stem cells”, – Kageyama says. “Only the expression dynamics differ between the two. A better understanding of the regulatory mechanisms of these different expression dynamics could allow us to switch the dormant cells on as part of a treatment for a range of neurological disorders.”