title: Early postnatal interference with the expression of multiple Sp1 regulated genes leads to disparate behavioral response to sub-chronic and chronic stress in rats.
abstract: BACKGROUND
  It is currently accepted that complex behavior and mental disorder results from a combination of biological susceptibility and exposure to environmental stimuli. Most of the gene-environment interaction models focus on the interaction between the stimuli and a single candidate gene. We suggest that an alternative approach is interference with the expression of multiple genes followed by exposure to environmental insults.
  
  
  METHODS
  Early interference with gene transcription was performed by treatment of 7 days old Wistar male rats for 4 days with the Sp1/DNA binding inhibitor, mithramycin. Environmental insult was mimicked by exposing these rats during adulthood (34 days) to sub-chronic (12 days, n=30) or chronic stress (28 days, n=48). The effects of mithramycin and stress treatment on the behavioral response and serum corticosterone concentration were assessed.
  
  
  RESULTS
  Exposure of mithramycin treated rats to sub-chronic stress led to anxious behavior in the open field test, high startle response, low sucrose preference, indifference to novel objects and high serum corticosterone concentration. However, exposure to chronic stress resulted in normal sucrose preference, startle response and serum corticosterone, novelty seeking behavior and reduced anxiety. In saline treated rats the extension of stress duration led to behavioral and hormonal adaptation to stress.
  
  
  CONCLUSIONS
  Our study suggests that postnatal temporal interference with multiple gene expression can lead to hyper-responsiveness to environmental stimuli, the features of which affects the phenotypic outcomes. Such a paradigm may be used to model gene-environmental interaction in the etiology of behavioral disorders.
authors.affiliation: Laboratory of Psychobiology, Department of Psychiatry, Rambam Medical Center and B. Rappaport Faculty of Medicine, Technion - IIT, Haifa 31096, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Asor
authors.forename: Hila
authors.initials: H
authors.lastname: Belhanes
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kavushansky
authors.forename: Salman
authors.initials: S
authors.lastname: Zubedat
authors.forename: Ehud
authors.initials: E
authors.lastname: Klein
authors.forename: Avi
authors.initials: A
authors.lastname: Avital
authors.forename: Dorit
authors.initials: D
authors.lastname: Ben-Shachar
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D002908:Chronic Disease; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D059647:Gene-Environment Interaction; D008297:Male; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D008926:Plicamycin / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D016329:Sp1 Transcription Factor / Q000502:physiology*; D013315:Stress, Psychological / Q000235:genetics / Q000503:physiopathology; D013997:Time Factors
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D016329:Sp1 Transcription Factor; D008926:Plicamycin
keywords: Gene–environmental interaction; Mental disorder; Mithramycin; Rats; Sp1; Stress