For many patients suffering from depressive illnesses the best pharmacological treatments are those that increase levels of serotonin, the brain chemical that regulates mood, sleep and memory. New research shows that a gene called p11 is closely related to serotonin transmission in the brain and may play a key role in determining a person’s susceptibility to the disease.
The investigators used a blind screen called a yeast two-hybrid screen to identify proteins that associate with the serotonin 1B receptor, a site known to play a role in depression and serotonin regulation. They found an association with a protein called p11, a protein previously identified as a regulator of the localization of several proteins on the cell’s surface.
The researchers analyzed tissue from a mouse model of depression as well as post-mortem tissue from depressed human patients, and found decreased levels of p11 protein in both cases. On the other hand, p11 levels increased in rats and mice that were treated with anti-depressant medications or electroconvulsive therapy.
To further test the connection the scientists genetically engineered two strains of mice: one that produced more p11 than normal and another that produced no p11 at all. They found that mice that overexpress p11 were hyperactive and, in a test designed to identify depression in rodents, acted just like mice that were on anti-depressant medication. Mice that lacked p11, meanwhile, acted depressed and showed less responsivity to anti-depressant medications.
Taken together, the findings point to p11 as a new target for developing depression treatments.
Per Svenningsson, a research assistant professor at Rockefeller University said: “Our findings demonstrate that patients with depression, and mice that model this disease, have decreased levels of p11 protein, and they suggest that drugs that increase p11 are likely to have anti-depressant properties.”