Analysis of target genes regulated by chronic electroconvulsive therapy reveals role for Fzd6 in depression

  • Voleti B
  • Tanis K
  • Newton S
 et al. 
  • 30

    Readers

    Mendeley users who have this article in their library.
  • 12

    Citations

    Citations of this article.

Abstract

Background: Chronic electroconvulsive seizure (chr-ECS), one of the most efficacious treatments for depressed patients, increases the levels of transcription factor cyclic adenosine monophosphate response element binding protein (CREB) in rodent models and mediates the effects of chronic antidepressant treatment. The objective of this study was to determine the changes in CREB occupancy at gene promoters and subsequent gene expression changes induced by chr-ECS. Methods: We use chromatin immunoprecipitation followed by microarray analysis to identify CREB binding promoters that are influenced by chr-ECS (n = 6/group). Selected genes are confirmed by secondary validation techniques, and the functional significance of one target was tested in behavioral models (n = 8/group) by viral mediated inhibition of gene expression. Results: The results demonstrate that chr-ECS enhances CREB binding and activity at a select population of genes in the hippocampus, effects that could contribute to the efficacy of chr-ECS. Viral vector-mediated inhibition of one of the CREB-target genes regulated by chr-ECS, Fzd6, produced anxiety and depressive-like effects in behavioral models of depression. Conclusions: The results identify multiple gene targets differentially regulated by CREB binding in the hippocampus after chr-ECS and demonstrate the role of Fzd6, a Wnt receptor in behavioral models of depression. © 2012 Society of Biological Psychiatry.

Author-supplied keywords

  • CREB
  • ChIP-chip
  • Wnt signaling
  • chr-ECS
  • depression
  • frizzled receptor

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Bhavya Voleti

  • Keith Q. Tanis

  • Samuel S. Newton

  • Ronald S. Duman

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free