It is obvious to everyone that disruptions in brain development increase the risk of problems further down the road. We have established a link to genetic contribution fairly quickly, but now scientists have come to point out that brain and mental illness can be caused by environmental factors as well. So, from embryogenesis to the formation of synapses in our nervous system, let’s explore how deviations from the precise process can alter the necessary cognitive, emotional, and behavioral functions.
Since we cannot study the actual human brain for clear ethical reasons, this study used human neural organoids, meaning an artificially grown tissue that resembles a part of the brain, which in this instance was unguided (combining cells from all different parts of the brain). We see more and more 3D in vitro cell models in scientific research. Those basically try to mimic the actual in vivo (in living organism) characteristics of the tissues we are trying to study.
To simulate the effect of stress, glucocorticoids were used. Glucocorticoids are steroid hormones produced from the cortex of adrenal glands, most of them linked to metabolic processes, but there are known stress hormones between them, where a well-known one could be cortisol. It is responsible for different aspects of our health as well, but mostly stress response regulation. Both high and low levels of cortisol can impact our health.
Transcriptional response to chronic glucocorticoid exposure during neural differentiation was characterized, and also to understand the underlying mechanisms, gene regulatory networks were studied by integrating single-cell transcriptomics, which in short allowed the scientists to pinpoint the effects in one individual cell.
As a result of this research, cell type–specific changes were found, including autism risk genes and several transcription factors associated with neurodevelopment. More closely, chronic glucocorticoid exposure influenced lineage specification by priming the inhibitory neuron lineage (through transcription factors like PBX3 - previously linked to tumor cell growth). Even with the evidence for this discovery, there is still more research to be done, mostly to further understand the underlying mechanisms of these changes. Until then, we can only wonder…
Resources:
Leander, D., et al. (2025) Chronic exposure to glucocorticoids amplifies inhibitory neuron cell fate during human neurodevelopment in organoids.
Chourpiliadis, C., Aeddula, N.R., (2023) Physiology, Glucocorticoids
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