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.

Highlights

  • Pregnant women at risk for preterm delivery are treated with high doses of synthetic glucocorticoids (GCs), such as dexamethasone or betamethasone, to enhance fetal lung maturation

  • We have focused on the effects of a single antenatal dex treatment on the development of the mouse hippocampus

  • After dex treatment apoptosis was increased in both the cornu ammonal (CA) and dentate gyrus (DG) and proliferation was reduced in the subgranular zone (SGZ) of the DG of the fetal hippocampus

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Summary

Introduction

Pregnant women at risk for preterm delivery are treated with high doses of synthetic glucocorticoids (GCs), such as dexamethasone (dex) or betamethasone, to enhance fetal lung maturation. This treatment is highly effective in reducing morbidity and mortality of the preterm neonate [1], increasing information is available about the adverse side effects of GC treatment. Acute administration of dex in rats results in neuronal death of granule cells in the DG, and pyramidal neurons in the cornu ammonal (CA) subfields of the hippocampus [6,7,8]. Many studies indicate a relationship between death and birth of neurons and suggest that neurogenesis does occur to maintain neuron numbers, especially after injury [15,16,17,18]

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