Subtle activation of a small subset of neurons in one region of the brain can make male mice resilient to, and even reverse, the detrimental effects of chronic stress. The same is true for female mice, but in a totally different region of the brain. Researchers at Penn State reported these findings in two studies in the journal Molecular Psychiatry and said the results could help explain the efficacy, or lack thereof, of certain antidepressant drugs and inform the development of new drugs and therapies.
The team developed a protocol to continuously activate neurons that produce the signaling molecule somatostatin, which help regulate several biological processes, in specific brain regions in mice. The researchers found that doing so in a region of the brain called the prelimbic cortex made male mice resilient to stress, but failed to do so in female mice. Doing so in the ventral hippocampus, a completely separate brain region, made female mice resilient, but not males. In a separate study, the team then compared the set of genes that are active in the prefrontal cortex of resilient and non-resilient mice before and after stress to understand the molecular mechanisms underlying these changes.
“Stress is a major contributor to vulnerability for psychiatric disorders like major depressive disorder and post-traumatic stress disorder,” said Bernhard Lüscher, professor of biology, biochemistry and molecular biology, and of psychiatry at Penn State and the leader of the research team.
Much like humans, stressed mice develop signs of anxiety and anhedonia,