Antenatal glucocorticoid treatment affects hippocampal development in mice

PLoS One. 2014 Jan 22;9(1):e85671. doi: 10.1371/journal.pone.0085671. eCollection 2014.

Abstract

Synthetic glucocorticoids are administered to pregnant women at risk for preterm delivery, to enhance fetal lung maturation. The benefit of this treatment is well established, however caution is necessary because of possible unwanted side effects on development of different organ systems, including the brain. Actions of glucocorticoids are mediated by corticosteroid receptors, which are highly expressed in the hippocampus, a brain structure involved in cognitive functions. Therefore, we analyzed the effects of a single antenatal dexamethasone treatment on the development of the mouse hippocampus. A clinically relevant dose of dexamethasone (0.4 mg/kg) was administered to pregnant mice at embryonic day 15.5 and the hippocampus was analyzed from embryonic day 16 until adulthood. We investigated the effects of dexamethasone treatment on anatomical changes, apoptosis and proliferation in the hippocampus, hippocampal volume and on total body weight. Our results show that dexamethasone treatment reduced body weight and hippocampal volume transiently during development, but these effects were no longer detected at adulthood. Dexamethasone treatment increased the number of apoptotic cells in the hippocampus until birth, but postnatally no effects of dexamethasone treatment on apoptosis were found. During the phase with increased apoptosis, dexamethasone treatment reduced the number of proliferating cells in the subgranular zone of the dentate gyrus. The number of proliferative cells was increased at postnatal day 5 and 10, but was decreased again at the adult stage. This latter long-term and negative effect of antenatal dexamethasone treatment on the number of proliferative cells in the hippocampus may have important implications for hippocampal network function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Body Weight / drug effects
  • Cell Count
  • Cell Proliferation / drug effects
  • Dexamethasone / adverse effects*
  • Female
  • Glucocorticoids / adverse effects*
  • Hippocampus / drug effects*
  • Hippocampus / embryology
  • Hippocampus / growth & development
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / cytology
  • Neurons / drug effects
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Time Factors

Substances

  • Glucocorticoids
  • Ki-67 Antigen
  • Dexamethasone

Grant support

Funding source: Hersenstichting Nederland, Grant number: 8F00(2).32. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.