Gene that changes the brain’s response to stress identified

The experiments homed in on the gene for a protein that, among other things, enhances the adaptability of neurons in the hippocampus, a brain region that plays a key role in mood, cognition and memory. When normal mice are exposed to chronic stress (simulated by confinement in a wire mesh restraint), there is a significant retraction in the projections, or dendrites, of some of the neurons in the hippocampus, which shrinks in overall volume as well. The new experiments, reported recently in Hippocampus, looked at mice that had only one instead of the usual two copies of the gene that produces BDNF. The researchers, from Rockefeller University and Weill Cornell Medical College, found that these mice had brains resembling those of normal mice after extended stress. In other words, stress did not have any effect on the experimental mice.

"The findings suggest that BDNF is one of the proteins that play a role in mediating the brain's plasticity," says Bruce S. McEwen, head of Rockefeller's Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology.

If researchers can find a way to deplete or supplement BDNF in adult mice, they may be able to answer the question of when in development, or even in adult life, it has the greatest impact. "What we're seeing is that there may be a developmental window for BDNF's role, or also that there may be a floor and a ceiling for the right amount of the protein that helps enable adaptive plasticity," McEwen says.

The new work adds to the understanding of BDNF's interaction with hormones in the brain. McEwen's lab recently discovered that a variant of the BDNF gene is a likely contender for a role in premenstrual disorders, changing mice's performance on certain memory tasks according to their stage of the estrous cycle.