You are currently viewing the abstract.
View Full TextLog in to view the full text
AAAS login provides access to Science for AAAS members, and access to other journals in the Science family to users who have purchased individual subscriptions.
Register for free to read this article
As a service to the community, this article is available for free. Existing users log in.
More options
Download and print this article for your personal scholarly, research, and educational use.
Buy a single issue of Science for just $15 USD.
This article has corrections. Please see:
- A Correction to the Research Article Titled: "Reversal of Depressed Behaviors in Mice by p11 Gene Therapy in the Nucleus Accumbens" by Brian Alexander, Jennifer Warner-Schmidt, Therese Eriksson, Carol Tamminga, Margarita Arango-Llievano, Subroto Ghose, Mary Vernov, Mihaela Stavarche, Sergei Musatov, Marc Flajolet, Per Svenningsson, Paul Greengard, Michael G. Kaplitt - October 27, 2010
- A Correction to the Research Article Titled: "Reversal of Depressed Behaviors in Mice by p11 Gene Therapy in the Nucleus Accumbens" by Brian Alexander, Jennifer Warner-Schmidt, Therese Eriksson, Carol Tamminga, Margarita Arango-Lievano, Subroto Ghose, Mary Vernov, Mihaela Stavarache, Sergei Musatov, Marc Flajolet, Per Svenningsson, Paul Greengard, Michael G. Kaplitt - December 15, 2010
Abstract
The etiology of major depression remains unknown, but dysfunction of serotonergic signaling has long been implicated in the pathophysiology of this disorder. p11 is an S100 family member recently identified as a serotonin 1B [5-hydroxytryptamine 1B (5-HT1B)] and serotonin 4 (5-HT4) receptor–binding protein. Mutant mice in which p11 is deleted show depression-like behaviors, suggesting that p11 may be a mediator of affective disorder pathophysiology. Using somatic gene transfer, we have now identified the nucleus accumbens as a key site of p11 action. Reduction of p11 with adeno-associated virus (AAV)–mediated RNA interference in the nucleus accumbens, but not in the anterior cingulate, of normal adult mice resulted in depression-like behaviors nearly identical to those seen in p11 knockout mice. Restoration of p11 expression specifically in the nucleus accumbens of p11 knockout mice normalized depression-like behaviors. Human nucleus accumbens tissue shows a significant reduction of p11 protein in depressed patients when compared to matched healthy controls. These results suggest that p11 loss in rodent and human nucleus accumbens may contribute to the pathophysiology of depression. Normalization of p11 expression within this brain region with AAV-mediated gene therapy may be of therapeutic value.
Footnotes
-
Citation: B. Alexander, J. Warner-Schmidt, T. M. Eriksson, C. Tamminga, M. Arango-Llievano, S. Ghose, M. Vernov, M. Stavarche, S. Musatov, M. Flajolet, P. Svenningsson, P. Greengard, M. G. Kaplitt, Reversal of depressed behaviors in mice by p11 gene therapy in the nucleus accumbens. Sci. Transl. Med. 2, 54ra76 (2010).
- Copyright © 2010, American Association for the Advancement of Science
