Antenatal glucocorticoid treatment affects hippocampal development in mice
Cornelle W Noorlander1, Deodata Tijsseling2, Ellen V S Hessel3
1Brain Center Rudolf Magnus, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands ; Department of Obstetrics, University Medical Center Utrecht, Utrecht, The Netherlands.
Plos One
|January 28, 2014
Summary
Antenatal dexamethasone, used to mature fetal lungs, transiently impacts mouse hippocampus development. Long-term, it reduces hippocampal cell proliferation, potentially affecting cognitive function.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Synthetic glucocorticoids like dexamethasone are given to pregnant women to promote fetal lung maturation.
- While beneficial, these steroids may cause adverse effects on fetal organ development, including the brain.
- Glucocorticoids act via corticosteroid receptors, highly present in the hippocampus, a region vital for cognitive functions.
Purpose of the Study:
- To investigate the effects of a single antenatal dexamethasone dose on mouse hippocampal development.
- To assess anatomical changes, apoptosis, proliferation, volume, and body weight following prenatal dexamethasone exposure.
Main Methods:
- Pregnant mice received a clinically relevant dose of dexamethasone (0.4 mg/kg) at embryonic day 15.5.
- Hippocampal development was analyzed from embryonic day 16 through adulthood.
- Evaluated parameters included body weight, hippocampal volume, cell apoptosis, and cell proliferation.
Main Results:
- Dexamethasone caused transient reductions in body weight and hippocampal volume, which resolved by adulthood.
- Increased hippocampal apoptosis was observed until birth, with no significant postnatal effects.
- Cell proliferation in the dentate gyrus subgranular zone was reduced during the apoptotic phase and showed long-term decrease in adulthood.
Conclusions:
- Antenatal dexamethasone exposure leads to transient developmental changes in the mouse hippocampus.
- A significant long-term reduction in hippocampal cell proliferation in adulthood was observed.
- This persistent effect on proliferation may have implications for hippocampal network function and cognitive abilities.
