Deleting Nf1 Protein Quickens Relief from Depression

Eliminating a certain protein encourages the birth of new nerve cells and allows antidepressants to take effect more quickly, according to an animal study in The Journal of Neuroscience.

The normal role of the protein, called neurofibromin 1, is to prevent uncontrolled cell growth. The study suggests that treatment strategies developed to stimulate nerve cell birth may help treat depression more quickly, as current antidepressants typically take several weeks to take full effect.

Specifically, a particular section of the hippocampus produces new nerve cells during a process known as neurogenesis. This is made possible by specialized cells called neural progenitor cells (NPCs). Although previous research has shown that adult neurogenesis declines with age and stress, therapies known to alleviate symptoms of depression, such as exercise and antidepressants, increase neurogenesis.

A team of scientists, led by Luis Parada, PhD, of the University of Texas Southwestern, studied neurogenesis after removing the neurofibromin 1 (Nf1) gene from NPCs in adult mice. Results revealed that the removal of Nf1 increased the number and maturation of newborn nerve cells in the adult hippocampus.

Then, following seven days of antidepressant treatment, Nf1 mutant mice showed fewer depressive- and anxiety-like behaviors, whereas mice without the mutation took longer to show improvements.

“Our findings establish an important role for Nf1 in controlling neurogenesis in the hippocampus and demonstrate that activation of adult NPCs is enough to regulate depression and anxiety-like behaviors,” said study co-author Renee McKay, PhD, of the University of Texas Southwestern.

“Our work is among the first to demonstrate the feasibility of altering mood via direct manipulation of adult neurogenesis,” McKay added.

To determine if removing Nf1 leads to long-term changes in mice, the scientists ran 8-month-old mice through a variety of tests developed to measure anxiety- and depressive-like behaviors.

The mutant mice showed fewer anxious behaviors and also demonstrated resistance to the effects of chronic mild, unpredictable stress. Furthermore, even without antidepressants, removing Nf1 from NPCs in adult mice decreased symptoms of depression and anxiety.

“This study demonstrates that inducing neurogenesis is sufficient to produce antidepressant behavioral actions, and provides novel targets for therapeutic interventions,” said Ronald Duman, PhD, a neurogenesis expert from Yale University.

From PsychCentral.com