With approximately 40 million people affected, epilepsy is one of the most common neurological disorders worldwide. Valproate is a commonly used medication for treating epilepsy and is also used to treat bipolar disorder. Because of the known increased risk of neurodevelopmental disorders such as autism spectrum disorders, special warnings apply to women of childbearing age who are taking valproate. However, research into exactly how the medication influences the mechanisms of early brain development has so far been insufficient. “For the first time, using laboratory-grown tissue models of the human brain, we investigated how the drug affects the cellular environment and how these changes, in turn, influence processes within individual cells,” explains Zeynep Yentür, a research associate in Professor’s Simone Mayer at the Zoological Institute (ZOO) at KIT. Simone Mayer is a postdoctoral fellow at the Youth Academy I HAdW.

Human brain organoids as a model system

For their study, the researchers used cerebral organoids. These are three-dimensional tissue structures grown from human stem cells that mimic various developmental stages of the prenatal brain. They treated these organoids with valproate for 30 days to simulate sustained exposure during early developmental stages. The researchers then examined the effects at the tissue, cellular, and molecular levels.

The results show that the drug significantly inhibits cell proliferation, disrupts the organized structure of key developmental regions, and impairs the ability of precursor cells to develop into mature neurons. The extracellular environment of the cells is particularly affected: it undergoes structural changes, becomes stiffer, and disrupts key communication and signaling processes that are essential for normal brain development. For some patients with epilepsy, valproate is the only effective treatment option despite the known risks. “Through our research, we aim to contribute to a better understanding of the drug’s mechanisms of action in order to enable new research approaches in the long term for minimizing risks to fetuses,” says Yentür. As a laboratory study using tissue models, the results do not replace clinical data but do provide important insights into fundamental developmental mechanisms.

Research in the 3D Matter Made to Order Cluster of Excellence

The study was conducted in collaboration between KIT, the Heidelberg Academy of Sciences and Humanities, the University of Tübingen, and the University of Heidelberg as part of the Cluster of Excellence 3D Matter Made to Order (3DMM2O). The 3DMM2O Cluster of Excellence, jointly sponsored by KIT and Heidelberg University, conducts research on three-dimensional additive manufacturing techniques—ranging from the molecular level to macroscopic dimensions. The goal is to produce components and systems using nanoprinting at the highest possible process speeds and resolutions, thereby laying the groundwork for novel applications in the materials and life sciences.

Original Publication

Yentür, Z., Branco, L., Sarieva, K., et al. Multiomics analysis identifies VPA-induced changes in neural progenitor cells, ventricular-like regions, and the cellular microenvironment in dorsal forebrain organoids. Molecular Psychiatry, 2026. DOI: 10.1038/s41380-026-03585-5


Contact for this press release
Leonie Kroll, Press Officer, Tel.: +49 1523 7740097, leonie kroll∂kit edu

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Original publication:

Yentür, Z., Branco, L., Sarieva, K. et al. Multiomics analysis identifies VPA-induced changes in neural progenitor cells, ventricular-like regions, and the cellular microenvironment in dorsal forebrain organoids. Molecular Psychiatry, 2026. DOI: 10.1038/s41380-026-03585-5 (https://www.nature.com/articles/s41380-026-03585-5)

Further information:

https://3dmm2o.de/ Further information on the 3DMM2O Cluster of Excellence
https://www.km.kit.edu/wissenschaftsjahr2026.php Additional publications related to the 2026 Year of Science “Medicine of the Future”

Model study on the antiepileptic drug valproate: Impact on early brain development | KIT / Model study on the antiepileptic drug valproate: Impact on early brain development Press releases from KIT and idw.