Stress hormones shift neuron types in the developing brain, study suggests

Infections, chemicals, stress—these environmental factors influence the risk of developing psychiatric or neurological disorders, especially if they occur before birth. The biological mechanisms behind this are still not fully understood.

Researchers investigated the impact of glucocorticoids, a type of steroid hormone, on the early stages of brain development. They found a shift in neuron types, showing that the developing brain is more susceptible to external influences than previously thought. Their findings have been published in Science Advances.

Glucocorticoids are part of the body’s natural stress response and are essential for normal fetal development. Therefore, if there is a risk of pre-term delivery, synthetic glucocorticoids are often prescribed during pregnancy to promote lung development. In fact, in 2020, 10% of all births (or 13 million newborns) were premature, making glucocorticoids a widely used medication around the world.

In the newly published study, Leander Dony and his colleagues at the Max Planck Institute of Psychiatry in Munich, headed by Elisabeth Binder, used brain organoids to test the effects of synthetic glucocorticoids on brain development. They worked in collaboration with research groups at the Karolinska Institutet in Stockholm and Helmholtz Munich, headed by Cristiana Cruceanu and Fabian Theis respectively.

Brain organoids are models of the developing brain that are derived from human stem cells and mature in a petri dish. In this study, organoids were exposed to synthetic glucocorticoids for an extended period of time, simulating excessive exposure during early pregnancy. The exposed organoids were then compared to unexposed, control organoids that were considered to follow a normal brain development path.

Shift in neuron types observed

The researchers’ main finding was a shift in the distribution of neuron types: In the exposed organoids, there was a higher proportion of inhibitory neurons and a lower proportion of excitatory neurons than in the unexposed organoids. Excitatory neurons cause the next neurons to fire, passing a signal on, while inhibitory neurons reduce the likelihood that the next neuron will fire, slowing a signal down.

“These results show us that the human brain is very malleable and susceptible to external influences during the early stages of development, even more so than we previously thought,” Dony states.

While an imbalance in neuron types has been linked to psychiatric and neurological disorders from a genetic perspective, this is the first study to show the same impact from environmental exposure. More research is needed to understand what the results of this study mean for disease risk: “We see an increased amount of inhibitory neurons, but our study results do not show us whether this means an increased risk or resilience to certain disorders later in life,” Cruceanu explains.

Brain organoids offer a unique opportunity for scientists to understand the development of the brain in its earliest stages. Knowing which factors influence disease risk later on in life, whether environmental factors, genetic risk factors or a combination thereof, can help to develop treatments and preventive measures in the future.