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 prescribed for bipolar disorder. Due to the known increased risk of neurodevelopmental disorders such as autism spectrum disorders, special warnings apply to women of childbearing age who take valproate. However, research into exactly how the drug influences the mechanisms of early brain development has been insufficient to date. “For the first time, we have used laboratory-grown tissue models of the human brain to investigate 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 Simone Mayer’s group at the Zoological Institute (ZOO) at KIT. Simone Mayer is a fellow at the Young Academy I HAdW.

Human brain organoids as a model system

The researchers used cerebral organoids for their study. These are three-dimensional tissue structures grown from human stem cells that replicate various developmental stages of the prenatal brain. They treated these organoids with valproate for 30 days to simulate prolonged exposure during early developmental phases. 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 zones, and impairs the development of precursor cells into mature neurons. The extracellular environment of the cells is particularly affected: it undergoes structural changes, becomes stiffer, and disrupts central 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. “With 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 provide important insights into fundamental developmental mechanisms.

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

The study was conducted in collaboration between KIT, the Heidelberg Academy of Sciences and Humanities, the University of Tübingen, and the University of Heidelberg within the Cluster of Excellence 3D Matter Made to Order (3DMM2O). The 3DMM2O Cluster of Excellence, jointly supported by KIT and Heidelberg University, investigates three-dimensional additive manufacturing techniques—from the molecular level to macroscopic dimensions. The goal is to produce components and systems using nanoprinting at the highest process speeds and resolutions, thereby creating the conditions for novel applications in 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 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.