Depressed Mice Just Need a Shot of Gene Therapy in the Brain

By Andrew Moseman | October 21, 2010 11:45 am

BrainBlackAccording to a new study out in Science Translational Medicine, treating depressed mice with gene therapy in the brain to bolster a protein connected to the neurotransmitter serotonin can make those depressive symptoms dissipate.

Here’s the gist: The gene in question creates a protein called p11 that help carry serotonin receptors up to the surface of a brain cell where they can receive signals from other brain cells. Poor serotonin signaling may be one of the major drivers behind depression, and a dearth of p11 could worsen the problem, according to study author Michael Kaplitt.

“In the absence of p11, a neuron can produce all the serotonin receptors it needs, but they will not be transported to the cell surface,” said Kaplitt. [AFP]

To test this, back in 2006 Nobel winner Paul Greengard (another coauthor on this study) created mice engineered to lack p11. Indeed, those mice developed the signs of severe depression. This time around, the team took similarly depressed mice and injected a reward center in their brain (the nucleus accumbens) with a virus that gave them a shot of p11. According to the researchers, the boost turned around the mice’s depression symptoms and they began to act like normal mice.

“Psychological disorders, such as depression, are increasingly viewed as brain disorders,” says study author Michael Kaplitt of the Weill Cornell Medical College in New York City. “If true, we may be able to help some patients by bringing levels of this protein back to normal.” [USA Today]

That said, the main criticisms of Kaplitt’s study note that depression is much more complicated than a single gene, protein, or receptor. And is a treatment as invasive as gene therapy on the brain really necessary for treating depression, or even effective against the most serious forms of the illness?

Because the treatment is invasive — requiring brain surgeons to drill into the skull and deliver the therapy to the right spot in the brain — it should only be used by severely afflicted patients that don’t respond to other drugs. “But that’s really not what the study tested,” says [Husseini] Manji, whose commentary on the study was also published in Science Translational Medicine today. The mice in the study might well have responded to Prozac, and it is not clear whether the treatment does treat the severest forms of the disorder. [Nature]

Worries aside, these types of therapies are on the horizon. The scientists involved in this study are also testing similar procedures for Parkinson’s disease. Kaplitt is working on a new project to test the p11 treatment in non-human primates, which could pave the way for human trials.

Related Content:
DISCOVER: Psychologist Says Antidepressants Are Just Fancy Placebos
80beats: Gene Therapy Hope for HIV: Engineered Stem Cells Hold Promise
80beats: Gene Therapy That Bulks up Muscles Raises Doping Concerns
80beats: Scientists See the Foreshadowing of Depression in Brain Anatomy

Image: iStockphoto

CATEGORIZED UNDER: Health & Medicine, Mind & Brain
  • Anton

    Interesting research, but I think we won’t defeat depression in humans that way.

  • Krokben

    Thanks! Nice read. I’ve been in treatment for depression for about 10 years and I would let them shoot me up with p11 any day. 😉 One question though:

    “the main criticisms of Kaplitt’s study note that depression is much more complicated than a single gene, protein, or receptor.”
    Is this backed up by some research or is it just an example of the fear of taking the human mind off of its holy throne? You know, the feeling in a lot of people that the mind (or is it ‘soul’?) is a grand and impenetrable mystery that science will never get to the heart of, so they’re afraid to find simple physical explenations for mental phenomena. I don’t think I’ve ever heard of a case of depression where the serotonin level was not low, so what’s to say that serotonin is not the main – or even the only – culprit? (I mean clinical depression here, not just sadness.)
    Even if the research is scarce I know there is at least some indication that DMT, while not helping the brain to produce serotonin, somehow makes the brain more receptive to the serotonin it already produces – and there are people who have reported getting rid of long term depression almost over night after taking DMT (extracted, or in one of it’s traditional forms, like ayahuasca). As far as I know there is no indication in these cases that anything besides serotonin is responsible for this on the level of the brain. Unfortunately most of what there is to read about DMT is not very scientific, but is new age nonsense from people who think it is an inherently spiritual substance allowing the soul to travel to different dimensions and times, meeting angels, aliens, demons, God, yourself etc – not to mention how it is responsible for the reincarnation of the soul in the pineal gland on the 49th day of fetal development.


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