No long-term effect two years after intrauterine exposure to dexamethasone on dentate gyrus volume, neuronal proliferation and differentiation in common marmoset monkeys

Abstract

Glucocorticoids are prenatally administered to promote the maturation of the lungs. They, however, can affect neuronal proliferation and differentiation. In newborn marmoset monkeys, intrauterine hyperexposure to dexamethasone (DEX) resulted in a significantly decreased proliferation rate in the hippocampal dentate gyrus without affecting neuronal differentiation. In this study, marmoset monkeys received 5 mg/kg body weight DEX either during early (days 42-48) or late (days 90-96) pregnancy. The volume of the dentate granule cell layer as well as the proliferation and neuronal differentiation in the dentate gyrus of their 2-year-old offspring were investigated. The density of proliferating cells (Ki-67), apoptotic cells (in situ tailing) and cells differentiating to neurons (double cortin, TUC-4 and calretinin) were determined immunohistochemically. Analysis of the dentate granule cell layer volume showed no significant differences between early or late DEX-exposed marmosets and untreated control animals. Similarly, proliferation and neuronal differentiation in DEX-treated animals was not significantly different in comparison with controls. In summary, the decreased proliferation rate observed in newborn marmosets after intrauterine exposure to DEX was no longer detectable in their 2-year-old siblings suggesting no long-lasting effect of prenatal hyperexposure to DEX on neuronal proliferation and differentiation in the dentate gyrus of marmoset monkeys.

Figure 1

A. Ki‐67‐immunoreactive neuron in the subgranular cell layer of the dentate gyrus (scale bar = 50 µm). B. Density of proliferating cells in the dentate gyrus of untreated and early and late dexamethasone‐exposed 2‐year‐old marmosets (medians ± 25%/75% percentiles, P = 0.93).

Figure 2

A. Four cells expressing the early neuronal marker doublecortin in the granule cell layer and subgranular cell layer of the dentate gyrus (scale bar = 50 µm). B. No significant changes in the density of doublecortin‐immunoreactive cells were observed between untreated and early and late dexamethasone‐exposed 2‐year‐old marmosets (medians ± 25%/75% percentiles, P = 0.09).

Figure 3

A. Cells expressing the early neuronal marker TUC‐4 in the granule cell layer of the dentate gyrus (scale bar = 50 µm). B. Comparison of the density of TUC‐4‐immunoreactive cells in the dentate gyrus of controls, early and late dexamethasone‐exposed 2‐year‐old marmoset revealed no significant differences (medians ± 25%/75% percentiles, P = 0.45).

Figure 4

A. Calretinin‐expressing cells in the subgranular cell layer of the dentate gyrus reflecting immature granule cells (scale bar = 50 µm). B. Density of calretinin‐immunoreactive cells in the dentate subgranular cell layer of controls, early and late dexamethasone‐exposed marmoset monkeys at the age of 2 years (medians ± 25%/75% percentiles, P = 0.49).

Figure 5

A. Apoptotic neuron (in situ tailing) in the subgranular cell layer of the dentate gyrus in 2‐year‐old marmoset monkey (scale bar = 50 µm). B. Density of apoptotic cells in the dentate gyrus of control marmosets and 2 years after early and late exposure to prenatal dexamethasone (medians ± 25%/75% percentiles, P = 0.8).