title: Analysis of target genes regulated by chronic electroconvulsive therapy reveals role for Fzd6 in depression.
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.
authors.affiliation: Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA.
authors.forename: Bhavya
authors.initials: B
authors.lastname: Voleti
authors.forename: Keith Q
authors.initials: KQ
authors.lastname: Tanis
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Newton
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Duman
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein; D047369:Chromatin Immunoprecipitation; D003863:Depression / Q000235:genetics* / Q000628:therapy; D004195:Disease Models, Animal; D004565:Electroconvulsive Therapy; D004924:Escape Reaction / Q000502:physiology; D005215:Fasting; D005518:Food Preferences / Q000502:physiology; D051157:Frizzled Receptors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D005822:Genetic Vectors / Q000502:physiology; D006624:Hippocampus; D006801:Humans; D008297:Male; D018782:Maze Learning; D046228:Microarray Analysis; D009043:Motor Activity / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: C484687:FZD6 protein, human; D051157:Frizzled Receptors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat