Disruptions in brain development are linked to higher risks of brain and mental illnesses. While genetics are known to play a role, environmental factors at the molecular and cellular levels have been less studied.
The international team of researchers from Karolinska Institutet, the Max Planck Institute of Psychiatry, and Helmholtz Munich aimed to understand how glucocorticoids — hormones involved in the body’s stress response and crucial for normal fetal development — affect brain development when overexposed.
The findings reveal that fetuses are more vulnerable to external influences like stress than previously thought. This stress can impact fetal brain development.
Cristiana Cruceanu, assistant professor at the Department of Physiology and Pharmacology, Karolinska Institutet, said, “We are interested in how environmental factors affect the developing brain, especially in the prenatal period. Previously, it was assumed that the uterus was like a bubble where nothing could get through. We now know that’s wrong. We are on a mission to find out what early life exposure to different factors could do to a human, focusing on brain development.”
When there’s a risk of pre-term delivery, synthetic glucocorticoids are often given during pregnancy to help develop the baby’s lungs. But how do these synthetic glucocorticoids affect the fetal brain?
To find out, researchers used brain organoids, which are 3D models of the developing brain created from human stem cells and grown in a petri dish. This allows them to simulate excessive exposure to glucocorticoids during early pregnancy. This advanced technology enables researchers to study these processes using a human-specific system without causing discomfort or harm to real humans or animals.
The researchers discovered that excessive exposure to glucocorticoids affects the fetal brain. They observed a change in the distribution of neuron types: the exposed organoids had more inhibitory neurons and fewer excitatory neurons than the unexposed organoids.
These results indicate that the developing brain is susceptible to external factors.
“We see an increased amount of inhibitory neurons, but our study results do not show whether this means an increased risk or resilience to certain disorders later in life,” Cruceanu explains.
“We know that stress, depression, and anxiety during pregnancy are common and that the need for treatment with medications like antidepressants comes in. Therefore, current work in my lab aims to study the effects of such medications on the developing brain. We want to know: Can the potentially negative effects of maternal stress be counteracted by antidepressant medications in the developing child – as it works for the mother? This is a complicated question to answer, but with organoids, we can control the exposure paradigms and look specifically at brain development”, concludes Cristiana Cruceanu.
Journal Reference:
- Leander Dony, Anthi C. Krontira, Lea Kaspar, Ruhel Ahmad, Ilknur Safak Demirel, Malgorzata Grochowicz, Tim Schäfer, Fatema Begum, Vincenza Sportelli, Catarina Raimundo, Maik Koedel, Marta Labeur, Silvia Capello, Fabian J.Theis, Cristiana Cruceanu and Elisabeth B. Binder. Chronic exposure to glucocorticoids amplifies inhibitory neuron cell fate during human neurodevelopment in organoids. Science Advances. DOI: 10.1126/sciadv.adn8631
Source: Tech Explorist
