Despite higher glucocorticoid levels and stress responses in female rats, both sexes exhibit similar stress-induced changes in hippocampal neurogenesis

Henriette J. Hulshof*, Arianna Novati, Paul G. M. Luiten, Johan A. den Boer, Peter Meerlo

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Sex differences in stress reactivity may be one of the factors underlying the increased sensitivity for the development of psychopathologies in women. Particularly, an increased hypothalamic-pituitary-adrenal (HPA) axis reactivity in females may exacerbate stress-induced changes in neuronal plasticity and neurogenesis, which in turn may contribute to an increased sensitivity to psychopathology. The main aim of the present study was to examine male-female differences in stress-induced changes in different aspects of hippocampal neurogenesis, i.e. cell proliferation, differentiation and survival. Both sexes were exposed to a wide variety of stressors, where after differences in HPA-axis reactivity and neurogenesis were assessed. To study the role of oestradiol in potential sex differences, ovariectomized females received low or high physiological oestradiol level replacement pellets. The results show that females in general have a higher basal and stress-induced HPA-axis activity than males, with minimal differences between the two female groups. Cell proliferation in the dorsal hippocampus was significantly higher in high oestradiol females compared to low oestradiol females and males, while doublecortin (DCX) expression as a marker of cell differentiation was significantly higher in males compared to females, independent of oestradiol level. Stress exposure did not significantly influence cell proliferation or survival of new cells, but did reduce DCX expression. In conclusion, despite the male-female differences in HPA-axis activity, the effect of repeated stress exposure on hippocampal cell differentiation was not significantly different between sexes. (C) 2012 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)357-364
Number of pages8
JournalBehavioral Brain Research
Issue number2
Publication statusPublished - 1-Oct-2012


  • sex differences
  • gender differences
  • cycle
  • oestradiol
  • estradiol
  • ovariectomy
  • psychopathology
  • stress
  • stress sensitivity
  • hypothalamic-pituitary-adrenal axis
  • HPA axis
  • stress hormones
  • ACTH
  • corticosterone
  • glucocorticoids
  • neuronal plasticity
  • hippocampus
  • dentate gyrus
  • neurogenesis
  • cell proliferation
  • BrdU

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