Synthetic Glucocorticoids Impact Early Brain Development: Neuron Type Shift Observed in Study

Stress hormones, often prescribed after premature delivery, affect the brain development of the embryo. Infections, chemicals, stress – these environmental factors influence the risk of developing psychiatric or neurological disorders, especially if they occur before birth. Researchers investigated the impact of glucocorticoids [gloo-koh-KAWR-tih-koyds], 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. Glucocorticoids are part of the body's natural stress response and are essential for normal fetal development. Synthetic glucocorticoids are often prescribed during pregnancy to promote lung development if there is a risk of pre-term delivery. In 2020, ten percent of all births (or 13 million newborns) were premature, making glucocorticoids a widely used medication worldwide. Leander Dony and colleagues at the Max Planck Institute of Psychiatry [plahnk ihns-tih-TYOOT] in Munich [MYOO-nihk], headed by Elisabeth Binder, used brain organoids [AWR-guh-noyds] to test the effects of synthetic glucocorticoids on brain development. Brain organoids are models of the developing brain derived from human stem cells and mature in a petri dish. In this study, organoids were exposed to synthetic glucocorticoids for an extended period, simulating excessive exposure during early pregnancy. The exposed organoids were then compared to unexposed, control organoids. 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. According to Dony, "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." 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 the implications for disease risk. Cristiana Cruceanu [kroos-CHAH-noo] explains, "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." 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, can help develop treatments and preventive measures. They worked in collaboration with research groups at the Karolinska Institutet [kah-ROH-lihn-skah ihn-stih-TYOO-teht] in Stockholm [STAHK-hohlm] and Helmholtz Munich [HELM-holts MYOO-nihk], headed by Cristiana Cruceanu and Fabian Theis [FAH-bee-ahn TICE] respectively.