It was already known that in rodents, the benefits of an active lifestyle for the brain, explains the author: "Laboratory animals that live in enriched environments, with wheels for exercise, toys and the presence of other animals, show better performance in memory and orientation tests, have more neurogenesis in the hippocampus, and also more dendritic spines, the structures of neurons that allow the formation of synapses or contacts between neuronal cells. And now, this work shows that the peripheral nervous system also benefits from an active lifestyle".

This finding explains why people who have led an "active lifestyle" recover more after spinal cord injury than those with "less active" lifestyles. Although the work is still at an early stage, the findings open a "realistic path" that tests the links between pre-existing active lifestyle and subsequent recovery from a spinal injury, and possibly paves the way for clinical trials in human patients, say researchers.

In addition, the researchers identified a key molecule in this process called CREB-Binding Protein (CBP), a regulator of gene expression that alters the expression of several genes, and thus increases the ability to regenerate damaged nerves.

Each cell of the human body contains a long strand of DNA, about two meters long, with genetic information. To fit inside the cell nucleus this DNA is wound on proteins called histones, forming a kind of pearl necklace. In order for genes to be expressed, the collar must unwind partially and accurately at the right time. And it is at this point where the CBP protein intervenes. CBP-mediated histone acetylation, which increased the expression of genes associated with the regenerative program.

The team has been working with the CBP protein for a long time, and they have a mouse model that lacks this protein in specific neuronal types. "By putting the deficient animals in CBP in an enriched environment, we saw that they are not able to respond to these stimuli and there is no increase in the repair of injuries," explains the author. Thanks to this animal model, it was clear that CBP is a key molecule, capable of becoming a therapeutic target to increase regeneration after spinal cord injury.

In tests with mice and rats, administering a compound that increases the activity of the CBP protein six hours after the injury of the column, and subsequently once a week, promoted the regeneration of the damaged nerve fibers. After the injury and treatment with the drug, the rats, which otherwise could not walk correctly, recovered significant mobility in their hind legs, compared to the control animals, without treatment.

Although this treatment may not be far from being tested in the clinic, more studies are needed to show that the drug is safe in humans. Once verified, it could potentially be combined with neurorehabilitation to treat people who have suffered a spinal cord injury.

https://stm.sciencemag.org/content/11/487/eaaw2064