Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Vulnerability versus resilience to prenatal stress in male and female rats; Implications from gene expression profiles in the hippocampus and frontal cortex

Van den Hove, D. L. A. ; Kenis, G. ; Brass, A. ; Opstelten, R. ; Rutten, B. P. F. ; Bruschettini, Matteo LU orcid ; Blanco, C. E. ; Lesch, K. P. ; Steinbusch, H. W. M. and Prickaerts, J. (2013) In European Neuropsychopharmacology 23(10). p.1226-1246
Abstract
Adverse life events during pregnancy may impact upon the developing fetus, predisposing prenatally stressed offspring to the development of psychopathology. In the present study, we examined the effects of prenatal restraint stress (PS) on anxiety- and depression-related behavior in both male and female adult Sprague-Dawley rats. In addition, gene expression profiles within the hippocampus and frontal cortex (FC) were examined in order to gain more insight into the molecular mechanisms that mediate the behavioral effects of PS exposure. PS significantly increased anxiety-related behavior in male, but not female offspring. Likewise, depression-related behavior was increased in male PS rats only. Further, male PS offspring showed increased... (More)
Adverse life events during pregnancy may impact upon the developing fetus, predisposing prenatally stressed offspring to the development of psychopathology. In the present study, we examined the effects of prenatal restraint stress (PS) on anxiety- and depression-related behavior in both male and female adult Sprague-Dawley rats. In addition, gene expression profiles within the hippocampus and frontal cortex (FC) were examined in order to gain more insight into the molecular mechanisms that mediate the behavioral effects of PS exposure. PS significantly increased anxiety-related behavior in male, but not female offspring. Likewise, depression-related behavior was increased in male PS rats only. Further, male PS offspring showed increased basal plasma corticosterone levels in adulthood, whereas both PS males and females had lower stress-induced corticosterone levels when compared to controls. Microarray-based profiling of the hippocampus and FC showed distinct sex-dependent changes in gene expression after PS. Biological processes and/or signal transduction cascades affected by PS included glutamatergic and GABAergic neurotransmission, mitogen-activated protein kinase (MAPK) signaling, neurotrophic factor signaling, phosphodiesterase (PDE)/ cyclic nucleotide signaling, glycogen synthase kinase 3 (GSK3) signaling, and insulin signaling. Further, the data indicated that epigenetic regulation is affected differentially in male and female PS offspring. These sex-specific alterations may, at least in part, explain the behavioral differences observed between both sexes, i.e. relative vulnerability versus resilience to PS in male versus female rats, respectively. These data reveal novel potential targets for antidepressant and mood stabilizing drug treatments including PDE inhibitors and histone deacetylase (HDAC) inhibitors. (C) 2012 Elsevier B.V. and ECNP. All rights reserved. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Prenatal stress, Depression, Anxiety, Microarray, Resilience, Epigenetics
in
European Neuropsychopharmacology
volume
23
issue
10
pages
1226 - 1246
publisher
Elsevier
external identifiers
  • wos:000325833500010
  • scopus:84884289212
  • pmid:23199416
ISSN
1873-7862
DOI
10.1016/j.euroneuro.2012.09.011
language
English
LU publication?
no
id
52c0cb16-8f04-4920-92b1-9af01d17d158 (old id 7856168)
date added to LUP
2016-04-01 10:31:24
date last changed
2022-02-17 18:52:23
@article{52c0cb16-8f04-4920-92b1-9af01d17d158,
  abstract     = {{Adverse life events during pregnancy may impact upon the developing fetus, predisposing prenatally stressed offspring to the development of psychopathology. In the present study, we examined the effects of prenatal restraint stress (PS) on anxiety- and depression-related behavior in both male and female adult Sprague-Dawley rats. In addition, gene expression profiles within the hippocampus and frontal cortex (FC) were examined in order to gain more insight into the molecular mechanisms that mediate the behavioral effects of PS exposure. PS significantly increased anxiety-related behavior in male, but not female offspring. Likewise, depression-related behavior was increased in male PS rats only. Further, male PS offspring showed increased basal plasma corticosterone levels in adulthood, whereas both PS males and females had lower stress-induced corticosterone levels when compared to controls. Microarray-based profiling of the hippocampus and FC showed distinct sex-dependent changes in gene expression after PS. Biological processes and/or signal transduction cascades affected by PS included glutamatergic and GABAergic neurotransmission, mitogen-activated protein kinase (MAPK) signaling, neurotrophic factor signaling, phosphodiesterase (PDE)/ cyclic nucleotide signaling, glycogen synthase kinase 3 (GSK3) signaling, and insulin signaling. Further, the data indicated that epigenetic regulation is affected differentially in male and female PS offspring. These sex-specific alterations may, at least in part, explain the behavioral differences observed between both sexes, i.e. relative vulnerability versus resilience to PS in male versus female rats, respectively. These data reveal novel potential targets for antidepressant and mood stabilizing drug treatments including PDE inhibitors and histone deacetylase (HDAC) inhibitors. (C) 2012 Elsevier B.V. and ECNP. All rights reserved.}},
  author       = {{Van den Hove, D. L. A. and Kenis, G. and Brass, A. and Opstelten, R. and Rutten, B. P. F. and Bruschettini, Matteo and Blanco, C. E. and Lesch, K. P. and Steinbusch, H. W. M. and Prickaerts, J.}},
  issn         = {{1873-7862}},
  keywords     = {{Prenatal stress; Depression; Anxiety; Microarray; Resilience; Epigenetics}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{1226--1246}},
  publisher    = {{Elsevier}},
  series       = {{European Neuropsychopharmacology}},
  title        = {{Vulnerability versus resilience to prenatal stress in male and female rats; Implications from gene expression profiles in the hippocampus and frontal cortex}},
  url          = {{http://dx.doi.org/10.1016/j.euroneuro.2012.09.011}},
  doi          = {{10.1016/j.euroneuro.2012.09.011}},
  volume       = {{23}},
  year         = {{2013}},
}