Early postnatal interference with the expression of multiple Sp1 regulated genes leads to disparate behavioral response to sub-chronic and chronic stress in rats

Eyal Asor, Hila Belhanes, Alexandra Kavushansky, Salman Zubedat, Ehud Klein, Avi Avital, Dorit Ben-Shachar

Research output: Contribution to journalArticlepeer-review

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. Conclusion: 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.

Original languageEnglish
Pages (from-to)2173-2183
Number of pages11
JournalPsychoneuroendocrinology
Volume38
Issue number10
DOIs
StatePublished - Oct 2013
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by a grant from the Rappaport Family Institute for Research in the Medical Sciences, Technion, Haifa Israel, and by Vincent Mayer Donation.

Funding Information:
This study was supported by a grant from the Rappaport Family Institute for Research in the Medical Sciences , Technion, Haifa Israel, and by Vincent Mayer Donation. None had any role in study design, in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Keywords

  • Gene-environmental interaction
  • Mental disorder
  • Mithramycin
  • Rats
  • Sp1
  • Stress

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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