Psy-World

The protein p11 plays a role in the antidepressant effect of brain-derived neurotrophic factor.

The protein p11, a member of the S100 family of calcium effector proteins, has been described as a key factor involved in both depressive-like states and antidepressant responses, through interaction with serotonin (5-hydroxytryptamine) receptors including 5-HT1B receptors. p11 is downregulated in postmortem tissue from depressed patients and is a mediator of responses to antidepressant drugs in rodents. p11 knockout mice have a depression-like phenotype and show a diminished behavioral response to antidepressants. A neurotrophic hypothesis of depression supports a role for brain-derived neurotrophic factor (BDNF) in the therapeutic activity of antidepressants. A study examined the possibility that BDNF could regulate p11 using in vitro and in vivo techniques in mice such as primary neuronal cultures, analyses of transgenic mice, and behavior. BDNF stimulated p11 expression through tropomyosin-related kinase B (trkB) receptors and via the mitogen-activated protein kinase signaling pathway. A correlation was found between BDNF-induced changes in p11 in vivo and changes in ligand binding to the 5-HT1B receptors, the subcellular localization of which is known to be regulated by p11. BDNF produced a statistically significant antidepressant-like effect in wild type mice that was not observed in p11 knockout mice in both the tail suspension test and the forced swim test. These results demonstrate that p11 levels are regulated by BDNF in vitro and in vivo, and suggest that the antidepressant activity of BDNF requires p11. This supports a role for p11 in the antidepressant activity of neurotrophins. Warner-Schmidt JL, Chen EY, Zhang X, Marshall JJ, Morozov A, Svenningsson P, Greengard P (2010). A Role for p11 in the Antidepressant Action of Brain-Derived Neurotrophic Factor. Biol Psychiatry, Jun 28, doi:10.1016/j.biopsych.2010.04.029 (in press). Updated August 2010