Stress experienced in utero reduces sexual dichotomies in neurogenesis, microenvironment, and cell death in the adult rat hippocampus

Chitra D. Mandyam, Elena F. Crawford, Amelia J. Eisen, Catherine L. Rivier, Heather N. Richardson

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Hippocampal function and plasticity differ with gender, but the regulatory mechanisms underlying sex differences remain elusive and may be established early in life. The present study sought to elucidate sex differences in hippocampal plasticity under normal developmental conditions and in response to repetitive, predictable versus varied, unpredictable prenatal stress (PS). Adult male and diestrous female offspring of pregnant rats exposed to no stress (control), repetitive stress (PS-restraint), or a randomized sequence of varied stressors (PS-random) during the last week of pregnancy were examined for hippocampal proliferation, neurogenesis, cell death, and local microenvironment using endogenous markers. Regional volume was also estimated by stereology. Control animals had comparable proliferation and regional volume regardless of sex, but females had lower neurogenesis compared to males. Increased cell death and differential hippocampal precursor kinetics both appear to contribute to reduced neurogenesis in females. Reduced local interleukin-1beta (IL-1β) immunoreactivity (IR) in females argues for a mechanistic role for the anti-apoptotic cytokine in driving sex differences in cell death. Prenatal stress significantly impacted the hippocampus, with both stress paradigms causing robust decreases in actively proliferating cells in males and females. Several other hippocampal measures were feminized in males such as precursor kinetics, IL-1β-IR density, and cell death, reducing or abolishing some sex differences. The findings expand our understanding of the mechanisms underlying sex differences and highlight the critical role early stress can play on the balance between proliferation, neurogenesis, cell death, and hippocampal microenvironment in adulthood.

Original languageEnglish (US)
Pages (from-to)575-589
Number of pages15
JournalDevelopmental Neurobiology
Volume68
Issue number5
DOIs
StatePublished - Apr 2008

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Neurogenesis
Sex Characteristics
Hippocampus
Cell Death
Interleukin-1beta
Cytokines
Pregnancy

Keywords

  • Apoptosis
  • Doublecortin
  • Interleukin-1 beta
  • Ki-67
  • Restraint and random stress
  • Sex differences
  • Subgranular zone

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

Stress experienced in utero reduces sexual dichotomies in neurogenesis, microenvironment, and cell death in the adult rat hippocampus. / Mandyam, Chitra D.; Crawford, Elena F.; Eisen, Amelia J.; Rivier, Catherine L.; Richardson, Heather N.

In: Developmental Neurobiology, Vol. 68, No. 5, 04.2008, p. 575-589.

Research output: Contribution to journalArticle

Mandyam, Chitra D. ; Crawford, Elena F. ; Eisen, Amelia J. ; Rivier, Catherine L. ; Richardson, Heather N. / Stress experienced in utero reduces sexual dichotomies in neurogenesis, microenvironment, and cell death in the adult rat hippocampus. In: Developmental Neurobiology. 2008 ; Vol. 68, No. 5. pp. 575-589.
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