The Journal of Science has published a research report which has identified the gene responsible for regulating memory, mood and sleep, and also plays an important role in determining a person's susceptibility to depression. For people suffering from depressive illnesses, the best pharmacological treatments are those that increase levels of serotonin. The gene, called p11, is closely related to serotonin transmission in the brain, and could lead to new treatments for mental disorders.
"We have shown that a gene called p11 is involved in the multiple complex changes that underlie depression. 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," said lead researcher Per Svenningsson.
The researchers used a blind screen called a yeast two-hybrid screen to identify proteins that associate with the serotonin 1B receptor. 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.
They 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 researchers 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 over express 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.
"In addition to exploring ways to increase p11 in depressed patients, it may also be possible to develop peptide-based compounds that can mimic the action of p11 to achieve a new class of anti-depressant compounds," said Svenningsson.