For the more than 18 million Americans who suffer 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 by an international team of scientists, led by Rockefeller University researchers in Nobel prize winner Paul Greengard’s laboratory, 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 depression.
The newly discovered link between depression and the serotonin system, reported in the January 6 issue of the journal Science, could lead to new treatments for these mental disorders.
“We have shown that a gene called p11 is involved in the multiple complex changes that underlie depression,” says Per Svenningsson, a research assistant professor and first-author on the paper. “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.”
Serotonin binds to 14 different receptors on a cell’s surface. One receptor in particular, known as 1B, plays a crucial role in regulating serotonin transmission in the brain. Recent studies have suggested a role for the serotonin 1B receptor in depression, as well as in obsessive-compulsive disorder, drug addiction, anxiety, aggression and sleep.
Intrigued by these studies, Svenningsson and colleagues at Rockefeller, the Karolinska Institute, the University of Rouen in France and Eli Lilly and Company, 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.
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, Svenningsson and his colleagues 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.
“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,” Svenningsson says.
Source: Rockefeller University
5 thoughts on “Scientists discover a protein linked to serotonin and depression”
It is hard to know how to respond to this news. Thanks for reporting it, first of all.
How do we know antidepressants are OK anyway?
Just a thought.
Keep up the good work.
Are there certain foods or supplements that nourish, more than others, the development of the protein P11?
I am curious as to how they think this works. Does P-11 do something to allow serotonin to more readily bind to the 1-B receptor?
I ask this because after years of suffering from depression, I’ve had enough and am trying to learn as much as possible about depression and serotonin and how things work- or don’t work. One thought that struck me as I was reading was if the treatment for depression- preventing the reuptake of serotonin- really was the best approach.
I’m not a neurobiologist- just a geek who reads- so I might be totally off base here but let me blunder along.
Does serotonin lose something/degrade when it either binds to a receptor or is floating around waiting to bind? And if so, does serotonin therefore undergoes a “refreshing” of sorts when it’s reuptaken by the neuron?
If that’s the case, then it would seem that blocking the reuptake would in the long-term cause more problems.
Wouldn’t a better approach be to produce more “fresh” serotonin?
The other question is how they think this P-11 works. Does it allow serotonin to bind more freely to the 1-B receptor? If that is the case, then you have to wonder if depression isn’t a question of the amount of serotonin or its reuptake, but if it is the result of some sort of problem with the 1-B receptors. Maybe there’s some sort of disorder akin to cancer where the signal gets scrambled and the receptor goes on the blink and will not allow serotonin to bind to it.
Just tossing this out there to shake things up a bit. Thanks for indulging me.
my question is that the p11 protein is bind to only 1B or all the receptor ?
I have been reading different information re:Annexin II up-regulates cellular levels of p11 protein by a post-translational mechanism.
Since this was done in 1995, are there any breakthroughs today as a result. Are there any studies in this area for people who are not responding to current treatments for severe depression to partake in?
I have a friend that said the on-set of her depression started at age 49 and that both of her parents suffered from a bi-polar disease. She is now 60 and in the grips of this depression and nothing is helping. What I have read makes sense and I am wondering if they are currently conducting research where she could partake and possibly benifit.