BACKGROUND: Despite recent interest in glycogen synthase kinase-3beta (GSK-3beta) as a target for the treatment of mood disorders, there has been very little work related to these illnesses on the upstream signaling molecules that regulate this kinase as well as downstream targets. METHODS: With a focused microarray approach we examined the influence of different classes of antidepressants on Wnt signaling that controls GSK-3beta activity as well as the transcription factors that contribute to the actions of GSK-3beta. RESULTS: The results demonstrate that Wnt2 is a common target of different classes of antidepressants and also show differential regulation of Wnt-GSK-3beta signaling genes. Increased expression and function of Wnt2 was confirmed by secondary measures. Moreover, with a viral vector approach we demonstrate that increased expression of Wnt2 in the hippocampus is sufficient to produce antidepressant-like behavioral actions in well-established models of depression and treatment response. CONCLUSIONS: These findings demonstrate that Wnt2 expression and signaling is a common target of antidepressants and that increased Wnt2 is sufficient to produce antidepressant effects. 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
BACKGROUND: Despite recent interest in glycogen synthase kinase-3beta (GSK-3beta) as a target for the treatment of mood disorders, there has been very little work related to these illnesses on the upstream signaling molecules that regulate this kinase as well as downstream targets. METHODS: With a focused microarray approach we examined the influence of different classes of antidepressants on Wnt signaling that controls GSK-3beta activity as well as the transcription factors that contribute to the actions of GSK-3beta. RESULTS: The results demonstrate that Wnt2 is a common target of different classes of antidepressants and also show differential regulation of Wnt-GSK-3beta signaling genes. Increased expression and function of Wnt2 was confirmed by secondary measures. Moreover, with a viral vector approach we demonstrate that increased expression of Wnt2 in the hippocampus is sufficient to produce antidepressant-like behavioral actions in well-established models of depression and treatment response. CONCLUSIONS: These findings demonstrate that Wnt2 expression and signaling is a common target of antidepressants and that increased Wnt2 is sufficient to produce antidepressant effects. 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Authors: S Fukumoto; C M Hsieh; K Maemura; M D Layne; S F Yet; K H Lee; T Matsui; A Rosenzweig; W G Taylor; J S Rubin; M A Perrella; M E Lee Journal: J Biol Chem Date: 2001-03-09 Impact factor: 5.157
Authors: Gary A Wayman; Soren Impey; Daniel Marks; Takeo Saneyoshi; Wilmon F Grant; Victor Derkach; Thomas R Soderling Journal: Neuron Date: 2006-06-15 Impact factor: 17.173
Authors: Dieter-Chichung Lie; Sophia A Colamarino; Hong-Jun Song; Laurent Désiré; Helena Mira; Antonella Consiglio; Edward S Lein; Sebastian Jessberger; Heather Lansford; Alejandro R Dearie; Fred H Gage Journal: Nature Date: 2005-10-27 Impact factor: 49.962
Authors: Melinda E Snitow; Giulia Zanni; Brianna Ciesielski; Pamela Burgess-Jones; Amelia J Eisch; W Timothy O'Brien; Peter S Klein Journal: Neurosci Lett Date: 2019-03-30 Impact factor: 3.046