# Effects of Prenatal Dexamethasone Treatment and Post-Weaning Moderate Fructose Intake on Synaptic Plasticity and Behavior in Adult Male Wistar Rat Offspring

## TL;DR

This study examines how prenatal dexamethasone treatment and post-weaning fructose intake affect brain development and behavior in adult male rats.

## Contribution

The study reveals that prenatal dexamethasone exposure influences synaptic plasticity and behavior, with fructose intake not altering these effects.

## Key findings

- Prenatal dexamethasone treatment increased exploratory behavior and reduced anxiety in adult rats.
- Fructose consumption after weaning did not modify the effects of prenatal dexamethasone exposure.
- Prenatal treatment increased levels of proteins related to synaptic plasticity and glucocorticoid receptors in the hippocampus.

## Abstract

During pregnancy, maternal glucocorticoids control fetal growth and the maturation of fetal tissues. Synthetic glucocorticoids are commonly used to stimulate lung differentiation in pregnancies at high risk of premature birth. Despite their beneficial effects on fetal survival, their impact on the developing brain is less clear. Among postnatal factors that might have a profound effect on both the cognitive capacity and behavior of the offspring, high fructose consumption in the young population is of particular concern. The present study aimed to investigate the effects of prenatal synthetic glucocorticoid exposure additionally challenged with postnatal fructose overconsumption on locomotion, anxiety, and memory in adult male rat offspring. According to our results, prenatal glucocorticoid treatment induced changes in reactions to novel situations in male rats that might represent advantageous fetal developmental adaptation, while increased exploratory behavior, reduced anxiety, and improved ability to recognize novel objects could improve survival in an adverse postnatal environment. On the other hand, moderate fructose consumption did not appear to alter the effects of prenatal glucocorticoid exposure, suggesting that fetal programming had a predominant influence.

Early-life glucocorticoid overexposure induces diverse neurodevelopmental outcomes regarding stress reactivity and cognition. Increased fructose consumption has also been associated with alterations in cognitive capacity and behavior. The present study investigated the effects of prenatal dexamethasone exposure on synaptic plasticity, locomotion, anxiety, and recognition memory in adult male Wistar rat offspring, and whether these effects are potentiated by postnatal fructose consumption. Pregnant female rats were treated with dexamethasone during late gestation and male offspring were supplemented with a moderate dose of fructose. Recognition memory, locomotion, and anxiety-like behavior were assessed using a novel object recognition test, open-field test, and elevated plus maze, respectively. Hippocampal synaptic plasticity was estimated by the levels of growth-associated protein 43 (GAP-43), synaptophysin, postsynaptic density protein 95, calcium/calmodulin-dependent kinase IIα, and their activating phosphorylations. Additionally, protein levels of the glucocorticoid receptor (GR) and its transcriptionally active phosphorylated form were evaluated. Prenatal dexamethasone treatment induced an anxiolytic-like effect, stimulation of exploratory behavior, and novelty preference associated with an increase in GR and GAP-43 protein levels in the hippocampus. Fructose overconsumption after weaning did not modify the effects of prenatal glucocorticoid exposure. Applied prenatal dexamethasone treatment may induce changes in reactions to novel situations in male Wistar rats.