Neurogenesis control by diazepam binding inhibitor!

Brain plasticity and its peptide mediator
Credit: Cell Stem Cell

The ability of the brain to respond and adapt to changes is scientifically called brain plasticity. This ability is the basis of all learning processes. New neurons, which can still be generated in the adult brain in specific areas, are instrumental in this process.

But until now it has been unknown which molecular processes translate environmental changes into the production of new neurons. Until a recent study conducted by few Scientists in Germany has led to the invention of a mediator, a first discovery of its kind. In the current study, a small peptide called Diazepam Binding Inhibitor (DBI) was identified, which is the key mediator in this process. The peptide was first identified because it binds to the receptor for a chemical messenger in the brain called Gamma- Amino Butyric Acid (GABA), where it replaces a drug called Diazepam (Valium).

A recent study reported that DBI promotes the development of new neurons in an area of the brain called subventricular zone. This brain area is responsible for the supply of new nerve cells in the olfactory system, which is particularly sophisticated in rodents. In the present study, researchers have shown that DBI has the same function in the hippocampus - the portion of the brain where memory formation and learning are located.

New neurons that form in the hippocampus improve orientation and learning capacity in the animals. Numerous research studies have already provided proof that in mice physical activity or variations in their environment stimulate neurogenesis in the hippocampus.

In this study,the researchers used  various genetic methods to turn off the DBI gene in this brain region in mice or, alternatively, to strongly boost it. When DBI was absent, the numbers of neural stem cells in the hippocampus declined. An oversupply of the peptide led to the presence of more neural stem and progenitor cells.

Equipping the cages with toys is an established method to stimulate the generation of new neurons in the hippocampus in rodents. However, in mice whose DBI gene had been silenced using molecular-biological tricks, the stimulating environment failed to have an effect: The quantities of neural stem cells could not be increased.

DBI exerts its effect by binding to the receptor for the chemical messenger GABA in the neural stem cells, thus acting as a molecular antagonist of this neurotransmitter. GABA is responsible for keeping the stem cells dormant in their niche without dividing. When DBI enters the scene, they start proliferating, thus enlarging the stem cell pool that is available as a reservoir for young neurons. In DBI, we seem to have found the key mediator. The peptide suppresses the effect of GABA and thus links the environmental stimuli to the production of new neurons that are required for learning.