After encountering trauma or severe stress, people develop an unusual stress response or chronic stress. This amplifies the risk of developing other diseases such as anxiety and depression, but it remains unknown what mechanisms are behind it or how the stress response is regulated mood.
Depression leads to suicide, when victims have such thoughts they have lower levels of the p11 protein in their brain, and laboratory mice with reduced p11 levels show depression – and anxiety – like behavior. The p11 levels in ice can also go up by some antidepressants.
According to the new study the p11 affects the initial discharge of the stress hormone cortisol in mice by adapting the activity of specific neurons in the brain area hypothalamus.
Through a wholly different signaling pathway begin in the brainstem, p11 also affects the release of two other stress hormones, adrenaline and noradrenalin. In addition, the tests showed that mice with p11 shortage react more strongly to stress, with a higher heart rate and more signs of anxiety, compared to mice with p11 levels.
“We know that an abnormal stress response can precipitate or worsen a depression and cause anxiety disorder and cardiovascular disease,” says first author Vasco Sousa, researcher at the Department of Clinical Neuroscience, Karolinska Institutet.
“Therefore, it is important to find out whether the link between p11 deficiency and stress response that we see in mice can also be seen in patients.”
The researchers believe that the findings may have implications for the development of new, more effective drugs. There is a great need for new treatments because current antidepressants are not effective enough in many patients.
“One promising approach involves administration of agents that enhance localised p11 expression, and several experiments are already being conducted in animal models of depression,” says Per Svenningsson, professor at the Department of Clinical Neuroscience, Karolinska Institutet, who led the study. “Another interesting approach which needs further investigation involves developing drugs that block the initiation of the stress hormone response in the brain.”