Project Overview

The hippocampus has the highest concentration of glucocorticoid receptors in the brain, and is therefore a primary target for glucocorticoids. The fetus may be exposed to increased levels of glucocorticoids as a result of maternal stress/anxiety, or by maternal treatment with synthetic glucocorticoids (sGC); ~10% of all pregnant women are at risk for premature labor and are administered sGC to mature the fetal lungs. Research from our lab has demonstrated that exposure to sGC during late gestation alters the  epigenetic and transcriptional profile of the fetal hippocampus. Most of the mechanistic research in this field utilizes animal models. It is imperative to determine whether the effects observed in animals translate to human cells and physiology. To address this issue, we will use a novel approach to assess the effects of cortisol (endogenous) and sGC exposure on human hippocampal neural progenitor cells (hNPC). Previous research has examined the effects of glucocorticoids on proliferation in human embryonic stem cells [5], but has yet to assess the actions of glucocorticoids on differentiated human hippocampal neurons. Our in vitro model will allow us to understand how glucocorticoids influence and shape the maturation of human hippocampal neurons in the fetal environment and how excess glucocorticoids alter the developmental trajectory of the brain.

Principal Investigator

Andrea Constantinof , University of Toronto

Partners and Donors

Azrieli Foundation

University of Toronto